An Overview of Diphtheria, Tetanus, and Pertussis Vaccines Manufactured by Sanofi Pasteur

I. Introduction

A. Diphtheria, Tetanus, and Pertussis: Etiology and Public Health Significance

Diphtheria, tetanus, and pertussis are serious infectious diseases that have historically imposed a significant burden on global public health. Understanding their etiology is crucial to appreciating the role of vaccination.

Diphtheria is an acute, toxin-mediated illness caused by toxigenic strains of the bacterium Corynebacterium diphtheriae. The bacterium typically colonizes the mucous membranes of the respiratory tract, leading to symptoms such as sore throat, fever, and the formation of a characteristic pseudomembrane, often in the pharynx or larynx. The primary virulence factor is diphtheria toxin, an exotoxin that inhibits protein synthesis in host cells, leading to tissue damage and potentially severe systemic complications, including myocarditis and neuropathy. Protection against diphtheria is primarily mediated by the presence of neutralizing antibodies against this toxin.[1] A serum diphtheria antitoxin level of

0.01 IU/mL is considered to confer some level of protection, while levels of ≥0.1 IU/mL are generally regarded as protective, and levels of 1.0 IU/mL are associated with long-term protection.[2]

Tetanus, also known as lockjaw, is an acute, often fatal, neurological disease caused by Clostridium tetani. This anaerobic bacterium is ubiquitous in soil and animal feces and typically enters the body through contaminated wounds. C. tetani produces a potent neurotoxin, tetanospasmin, which affects the central nervous system by blocking inhibitory neurotransmitters, leading to uncontrolled muscle spasms and rigidity. Symptoms can include trismus (lockjaw), opisthotonos (arching of the back), and respiratory muscle paralysis. Protection against tetanus is achieved through the development of neutralizing antibodies to tetanus toxin.[2] A serum tetanus antitoxin level of

≥0.01 IU/mL (measured by neutralization assay) is considered the minimum protective level, with levels ≥0.1 IU/mL (often measured by ELISA) generally considered protective.[2]

Pertussis, or whooping cough, is a highly contagious respiratory infection caused by the Gram-negative coccobacillus Bordetella pertussis. The bacterium attaches to the cilia of respiratory epithelial cells, producing toxins that damage the respiratory tract and lead to the characteristic paroxysmal cough, often followed by an inspiratory "whoop." Pertussis can be particularly severe, and even fatal, in infants who are too young to be fully vaccinated. While B. pertussis produces various biologically active components, including pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae (FIM), their precise roles in the pathogenesis of the disease or in conferring immunity are not fully elucidated, and a definitive serological correlate of protection remains unestablished.[2]

Prior to the widespread implementation of vaccination programs, these three diseases caused substantial morbidity and mortality worldwide, particularly among children. The introduction and consistent use of vaccines have dramatically reduced their incidence, transforming them from common childhood scourges to largely preventable conditions in many parts of the world. However, outbreaks can still occur, especially in populations with suboptimal vaccination coverage, underscoring the continued importance of maintaining high immunization rates.

B. The Role of Vaccination in Disease Prevention

Vaccination stands as the cornerstone of public health strategies for the control and prevention of diphtheria, tetanus, and pertussis. The vaccines work by inducing active immunity. This process involves introducing specific antigens (inactivated toxins, known as toxoids, for diphtheria and tetanus; and purified components of the bacterium for acellular pertussis vaccines) into the body. These antigens stimulate the immune system to produce a protective response, primarily through the generation of specific antibodies, without causing the disease itself. Upon subsequent exposure to the actual pathogens or their toxins, the vaccinated individual's immune system can mount a rapid and robust defense, preventing or mitigating the severity of the illness. The success of DTP vaccination programs is evident in the precipitous decline in disease incidence observed globally over the past several decades.

C. Sanofi Pasteur: A Key Contributor to Diphtheria, Tetanus, and Pertussis Vaccines

Sanofi Pasteur, the vaccines division of Sanofi, is a leading global manufacturer and supplier of a wide range of vaccines, playing a pivotal role in the fight against infectious diseases. The company has a long-standing history in the development and production of vaccines targeting diphtheria, tetanus, and pertussis. Its portfolio includes a variety of formulations designed to meet the immunization needs of diverse populations, from infants to adults.[5]

The range of diphtheria, tetanus, and pertussis (DTP)-containing vaccines offered by Sanofi Pasteur reflects a significant evolution in vaccine technology and public health strategy. The company provides DTaP (Diphtheria, Tetanus, acellular Pertussis) vaccines for primary immunization in infants and young children, such as DAPTACEL®, and Tdap (Tetanus, reduced diphtheria, acellular Pertussis) vaccines like Adacel® for adolescent and adult booster doses, including use in pregnant women. Additionally, Td (Tetanus, reduced diphtheria) vaccines like Tenivac® are available for older children and adults. Beyond these, Sanofi Pasteur has been instrumental in developing and marketing complex combination vaccines, such as Pentacel®, Quadracel®, and Vaxelis® (in partnership), which incorporate antigens for other preventable diseases like poliomyelitis (IPV), Haemophilus influenzae type b (Hib), and Hepatitis B (HepB).[5]

This progression from single or few-antigen vaccines to multi-component combination vaccines is a deliberate response to several public health imperatives. A primary driver has been the continuous effort to improve vaccine safety, exemplified by the shift from whole-cell pertussis (wP) components, which were associated with higher rates of local and systemic reactions, to less reactogenic acellular pertussis (aP) components. Concurrently, enhancing vaccine efficacy through optimized antigen selection and formulation has been a constant goal. Perhaps one of the most impactful advancements has been the development of combination vaccines. These formulations address the challenge of an increasingly crowded pediatric immunization schedule by reducing the total number of injections required to protect against multiple diseases.[7] For instance, Quadracel® was specifically developed to consolidate the final DTaP and IPV doses into a single shot for preschool children.[1] Reducing the injection burden is not merely a matter of convenience; it can significantly improve parental acceptance of vaccination and adherence to recommended schedules, which are critical for achieving and maintaining high population immunity. Sanofi Pasteur's diverse and evolving DTP vaccine portfolio thus demonstrates a sustained commitment to refining immunization practices, enhancing vaccine safety and immunogenicity, and improving the overall vaccination experience, thereby making substantial contributions to the global control of these important diseases.

II. Overview of Sanofi Pasteur's Diphtheria, Tetanus, and Pertussis (DTP)-Containing Vaccine Portfolio

A. Categorization of Sanofi Pasteur's DTP-Containing Vaccines

Sanofi Pasteur's DTP-containing vaccine offerings can be broadly categorized based on their antigen composition, intended age groups, and specific roles within immunization schedules. These categories include:

• DTaP (Diphtheria and Tetanus Toxoids and Acellular Pertussis) Vaccines: These vaccines contain full-strength diphtheria and tetanus toxoids combined with multiple purified acellular pertussis antigens. They are primarily intended for the primary immunization series in infants and young children, as well as for booster doses in early childhood. DAPTACEL® is Sanofi Pasteur's standalone DTaP vaccine.[5]
• Tdap (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis) Vaccines: These are booster vaccines formulated with a reduced quantity of diphtheria toxoid and, in some cases, reduced quantities of certain pertussis antigens compared to DTaP vaccines. This reduction aims to minimize reactogenicity in older individuals who may have pre-existing immunity. Tdap vaccines are indicated for adolescents and adults, including pregnant women to provide passive protection to newborns. Adacel® is Sanofi Pasteur's Tdap vaccine.[3]
• Td (Tetanus and Diphtheria Toxoids Adsorbed) Vaccines: These vaccines contain tetanus toxoid and a reduced quantity of diphtheria toxoid. They are used as booster doses for older children and adults to maintain immunity against tetanus and diphtheria. Pertussis antigens are not included in Td vaccines. Tenivac® is Sanofi Pasteur's Td vaccine.[5]
• Combination Vaccines: Sanofi Pasteur has developed and markets several DTaP-based combination vaccines that include antigens for other diseases. These vaccines are designed to simplify immunization schedules by reducing the number of injections required. Examples include:
• Pentacel®: A DTaP-IPV/Hib vaccine, combining DTaP with inactivated poliovirus vaccine (IPV) and Haemophilus influenzae type b (Hib) conjugate vaccine.[5]
• Quadracel®: A DTaP-IPV vaccine, combining DTaP with IPV, typically used for the preschool booster dose.[1]
• Vaxelis®: A DTaP-IPV-Hib-HepB vaccine, a hexavalent formulation also including Hepatitis B vaccine, developed and marketed through a partnership (MCM Vaccine Company, a joint venture between Sanofi Pasteur and Merck).[5]

This diverse portfolio allows healthcare providers to select the most appropriate vaccine based on an individual's age, vaccination history, and specific immunization needs, aligning with comprehensive public health recommendations.

B. Table 1: Summary of Key Sanofi Pasteur Diphtheria, Tetanus, and Pertussis-Containing Vaccines

To provide a concise overview of the primary DTP-containing vaccines manufactured or marketed by Sanofi Pasteur, the following table summarizes their key characteristics. This allows for a quick comparison of their types, antigens, and primary approved age groups, facilitating initial reference for healthcare professionals.

Brand Name	Vaccine Type	Key Antigens Protected Against	Primary Approved Age Group(s)	Manufacturer Notes
DAPTACEL®	DTaP	Diphtheria, Tetanus, Pertussis	Infants and children 6 weeks through 6 years of age (prior to 7th birthday) for a 5-dose series.2	Sanofi Pasteur
Adacel®	Tdap	Tetanus, Diphtheria (reduced), Pertussis (acellular)	Persons 10 through 64 years of age for active booster immunization. Also for immunization during the third trimester of pregnancy to prevent pertussis in infants younger than 2 months of age.3	Sanofi Pasteur
Pentacel®	DTaP-IPV-Hib	Diphtheria, Tetanus, Pertussis, Poliomyelitis, invasive disease due to Haemophilus influenzae type b	Children 6 weeks through 4 years of age (prior to 5th birthday) for a 4-dose series.9	Sanofi Pasteur
Quadracel®	DTaP-IPV	Diphtheria, Tetanus, Pertussis, Poliomyelitis	Children 4 through 6 years of age as a fifth dose in the DTaP series and as a fourth or fifth dose in the IPV series, particularly for those whose previous DTaP doses were with Pentacel®, DAPTACEL®, and/or VAXELIS®.1	Sanofi Pasteur
Tenivac®	Td	Tetanus, Diphtheria (reduced)	Persons 7 years of age and older for primary immunization (if unimmunized), routine booster immunization, diphtheria prophylaxis for case contacts, and tetanus prophylaxis in wound management.4	Sanofi Pasteur
Vaxelis®	DTaP-IPV-Hib-HepB	Diphtheria, Tetanus, Pertussis, Poliomyelitis, Hepatitis B, invasive disease due to H. influenzae type b	Children 6 weeks through 4 years of age (prior to the 5th birthday) for a 3-dose series. Note: A 3-dose series of VAXELIS® does not constitute a primary immunization series against pertussis; an additional dose of pertussis-containing vaccine is needed.7	MCM Vaccine Company (Sanofi Pasteur and Merck partnership)

Data compiled from sources:.[1]

III. Detailed Profiles of Specific Sanofi Pasteur Vaccines

This section provides detailed information on individual Diphtheria, Tetanus, and Pertussis (DTP)-containing vaccines manufactured or marketed by Sanofi Pasteur, covering their composition, indications, dosage, mechanism of action, safety profile, and immunogenicity.

A. DAPTACEL® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed)

1. Composition and Formulation

Each 0.5 mL dose of DAPTACEL® is formulated to contain the following active ingredients: 15 Lf (limit of flocculation units) of diphtheria toxoid, 5 Lf of tetanus toxoid, and acellular pertussis antigens. The pertussis components include 10 µg of detoxified pertussis toxin (PT), 5 µg of filamentous hemagglutinin (FHA), 3 µg of pertactin (PRN), and 5 µg of fimbriae types 2 and 3 (FIM).[5]

Other ingredients per 0.5 mL dose include 1.5 mg of aluminum phosphate (equivalent to 0.33 mg of aluminum) which acts as an adjuvant to enhance the immune response. The formulation also contains ≤5 µg of residual formaldehyde, <50 ng of residual glutaraldehyde, and 3.3 mg (0.6% v/v) of 2-phenoxyethanol, which is present but not as a preservative.[5]

The quantities of pertussis antigens in DAPTACEL® are notable when compared to other DTaP-containing combination vaccines from Sanofi Pasteur or its partnerships. For instance, Pentacel® and VAXELIS® contain twice the amount of detoxified PT (20 µg) and four times the amount of FHA (20 µg) compared to DAPTACEL®.[2] Quadracel® also contains these higher amounts of PT and FHA (

20 µg each), similar to Pentacel®.[1] These variations in antigen content could theoretically influence the magnitude or breadth of the immune response to specific pertussis components. However, all these vaccines are formulated and licensed based on demonstrated safety and immunogenicity. The U.S. Food and Drug Administration (FDA) prescribing information for DAPTACEL® explicitly states that it can be used as any of the doses in a 5-dose DTaP series that was initiated with Pentacel® or VAXELIS®.[2] This regulatory acceptance of interchangeability for series completion, despite quantitative differences in some antigens, suggests that the resulting immune responses are considered adequately protective. Nevertheless, these differences underscore the complexity of vaccine formulation and the importance of adhering to specific product labeling for completing immunization series, particularly as data on mixed sequences with DTaP vaccines from different manufacturers are often limited.[2]

2. Indications and Usage

DAPTACEL® is indicated for active immunization against diphtheria, tetanus, and pertussis. It is approved for use as a five-dose series in infants and children 6 weeks through 6 years of age (i.e., prior to their 7th birthday).[2] DAPTACEL® is not indicated for use in infants younger than 6 weeks of age or in children 7 years of age or older.[2]

3. Dosage and Administration

The immunization series for DAPTACEL® consists of five 0.5 mL intramuscular injections.[2]

The recommended schedule for administration is as follows:

• Dose 1: At 2 months of age (can be given as early as 6 weeks of age).
• Dose 2: At 4 months of age.
• Dose 3: At 6 months of age.
• The interval between the first three doses should ideally be 6 to 8 weeks.[2]
• Dose 4: At 15-20 months of age.
• Dose 5: At 4-6 years of age.[2]

The first four doses of DAPTACEL® constitute a primary immunization course for pertussis, with the fifth dose serving as a booster for pertussis immunization. For diphtheria and tetanus, the first three doses constitute a primary immunization course, while the fourth and fifth doses act as boosters.[2]

DAPTACEL® is for intramuscular injection only. Before administration, the vial should be shaken well until a uniform, white, cloudy suspension is observed. A single 0.5 mL dose should be withdrawn and administered intramuscularly, and any unused portion should be discarded. A separate sterile needle and syringe must be used for each injection. For infants younger than 1 year, the anterolateral aspect of the thigh is the preferred injection site due to its larger muscle mass. In older children, the deltoid muscle of the upper arm is typically adequate. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk. DAPTACEL® must not be administered intravenously or subcutaneously, and it should not be combined through reconstitution or mixed with any other vaccine in the same syringe or vial.[2]

Regarding mixed immunization schedules, DAPTACEL® contains the same pertussis antigens, manufactured by the same process, as Pentacel® and VAXELIS®. As noted, Pentacel® and VAXELIS® contain higher amounts of detoxified PT and FHA than DAPTACEL®. Despite these differences, DAPTACEL® may be used as any of the doses in a 5-dose DTaP series initiated with Pentacel® or VAXELIS®.[2] However, data on the safety and effectiveness of using mixed sequences of DAPTACEL® and DTaP-containing vaccines from different manufacturers for successive doses are not available.[2]

4. Mechanism of Action

DAPTACEL® works by stimulating the recipient's immune system to produce active immunity against diphtheria, tetanus, and pertussis.

• Diphtheria: The diphtheria toxoid component induces the production of neutralizing antibodies against diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is considered to provide some measure of protection, while levels of at least 0.1 IU/mL are generally considered protective. Higher levels, such as 1.0 IU/mL, have been associated with long-term protection.[2]
• Tetanus: The tetanus toxoid component stimulates the development of neutralizing antibodies against tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL (as measured by a neutralization assay) is recognized as the minimum protective level. Levels ≥0.1 IU/mL (often measured by ELISA) are considered protective.[2]
• Pertussis: The acellular pertussis components (PT, FHA, PRN, and FIM) induce an immune response against Bordetella pertussis. While the exact immunological correlates of protection against pertussis are not clearly defined, the efficacy of DTaP vaccines containing these antigens has been demonstrated in clinical trials.[2]

5. Contraindications

DAPTACEL® is contraindicated under the following conditions:

• Severe Allergic Reaction (Hypersensitivity): A history of a severe allergic reaction (e.g., anaphylaxis) to a previous dose of DAPTACEL®, or any other diphtheria toxoid, tetanus toxoid, or pertussis-containing vaccine, or to any component of DAPTACEL®. If such a reaction occurs, none of the components should be administered due to uncertainty about the specific causative agent. Consultation with an allergist may be appropriate if further immunizations are considered.[2]
• Encephalopathy: Occurrence of encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause is a contraindication to the administration of any pertussis-containing vaccine, including DAPTACEL®.[2]
• Progressive Neurologic Disorder: DAPTACEL® is contraindicated in individuals with a progressive neurologic disorder, such as infantile spasms, uncontrolled epilepsy, or progressive encephalopathy. Vaccination should be deferred until a treatment regimen has been established and the underlying condition has stabilized.[2]

6. Warnings and Precautions

Several warnings and precautions should be considered before administering DAPTACEL®:

• Management of Acute Allergic Reactions: As with any injectable vaccine, epinephrine hydrochloride solution (1:1,000) and other appropriate agents and equipment must be readily available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.[2]
• Adverse Reactions Following Prior Pertussis Vaccination: If certain adverse events occurred after a previous dose of a whole-cell pertussis or acellular pertussis component vaccine, the decision to administer DAPTACEL® should be based on careful consideration of the potential benefits and risks. These events include:
• Fever ≥40.5∘C (≥105∘F) within 48 hours, not attributable to another identifiable cause.
• Collapse or shock-like state (hypotonic-hyporesponsive episode [HHE]) within 48 hours.
• Persistent, inconsolable crying lasting ≥3 hours, occurring within 48 hours.
• Seizures with or without fever occurring within 3 days.[2]
• Guillain-Barré Syndrome (GBS) and Brachial Neuritis: If GBS occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the risk for GBS may be increased following DAPTACEL®. The Institute of Medicine found evidence for a causal relation between tetanus toxoid and both GBS and brachial neuritis.[2]
• Infants and Children with a History of Previous Seizures: For infants or children with a history of previous seizures, an appropriate antipyretic (e.g., acetaminophen) may be administered at the time of DAPTACEL® vaccination and for the following 24 hours to reduce the possibility of post-vaccination fever, which could trigger a seizure.[2]
• Limitations of Vaccine Effectiveness: Vaccination with DAPTACEL® may not protect all susceptible individuals.[2]
• Altered Immunocompetence: If DAPTACEL® is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the expected immune response may not be obtained or may be diminished.[2]
• Apnea in Premature Infants: Apnea following intramuscular vaccination has been observed in some infants born prematurely. The decision to administer DAPTACEL® to a premature infant should be based on the individual infant’s medical status and a careful assessment of the potential benefits and possible risks of vaccination.[2]
• Syncope: Syncope (fainting) can occur in association with the administration of injectable vaccines, including DAPTACEL®. Procedures should be in place to prevent injury from fainting.[2]

7. Adverse Reactions

The safety profile of DAPTACEL® has been evaluated in numerous clinical trials. Adverse reaction rates can vary by dose number.

• Clinical Trials Experience:
• Systemic Reactions: Following doses 1 through 3, the most frequently reported systemic reactions (occurring in >50% of subjects in US studies) included fussiness/irritability, inconsolable crying, and decreased activity/lethargy. Fever ≥38.0∘C occurred in 6-16% of US subjects, depending on the dose number.[2]
• Injection Site Reactions: These were most frequently reported following doses 4 and 5. Reactions occurring in >30% of subjects after any dose included tenderness, redness, and an increase in arm circumference.[2]
• Sweden I Efficacy Trial (Doses 1-3): In this trial, infants receiving DAPTACEL® at 2, 4, and 6 months of age experienced rates of local and systemic reactions within 24 hours that were similar to those observed in recipients of a Diphtheria-Tetanus (DT) vaccine and significantly lower than rates in infants who received a whole-cell pertussis DTP vaccine. Specific rates for tenderness (8.0-10.8%), redness ≥2 cm (0.3-3.7%), swelling ≥2 cm (0.9-6.3%), fever ≥38∘C (7.8-23.6%), fretfulness (32.3-39.6%), anorexia (8.4-11.2%), drowsiness (18.9-32.7%), crying ≥1 hour (1.2-2.5%), and vomiting (4.3-6.9%) were reported, varying by dose.[2]
• US Studies (Doses 4 & 5): The incidence of redness, tenderness, and swelling at the DAPTACEL® injection site generally increased with the fourth and fifth doses, with the highest rates observed after the fifth dose.[2]

The following table summarizes common solicited adverse reactions observed in US clinical trials for DAPTACEL®, stratified by dose number, providing quantitative data valuable for counseling parents and guardians.

Table 2: Common Solicited Adverse Reactions within 0-3 Days Following DAPTACEL® Administration in US Studies (% of Subjects)

Adverse Reaction	Dose 1 (N range)	Dose 2 (N range)	Dose 3 (N range)	Dose 4 (N range)	Dose 5 (DAPTACEL-primed, N range)	Dose 5 (Pentacel-primed, N range)
Injection Site Reactions
Redness >5 mm	6.2% (N=1105)	7.1% (N=983)	9.6% (N=933)	17.3% (N=688)	35.8% (N=243)	20.2% (N=238)
Swelling >5 mm	4.0% (N=1105)	4.0% (N=983)	6.5% (N=933)	11.7% (N=688)	23.9% (N=243)	12.0% (N=238)
Tenderness (Any)	48.8% (N=1105)	38.2% (N=983)	40.9% (N=933)	49.5% (N=688)	61.5% (N=243)	50.0% (N=238)
Increase in Arm Circumference >5 mm	N/A	N/A	N/A	30.1% (N=688)	38.3% (N=243)	28.6% (N=238)
Interference with Arm Activity	N/A	N/A	N/A	N/A	20.4% (N=243)	8.8% (N=238)
Systemic Reactions
Fever ≥38.0∘C	9.3% (N=1105)	16.1% (N=983)	15.8% (N=933)	10.5% (N=688)	6.1% (N=243)	4.6% (N=238)
Decreased Activity/Lethargy (Any)	51.1% (N=1105)	37.4% (N=983)	33.2% (N=933)	25.3% (N=688)	21.0% (N=243)	12.6% (N=238)
Inconsolable Crying (Any)	58.5% (N=1105)	51.4% (N=983)	47.9% (N=933)	37.1% (N=688)	14.1% (N=243)	7.2% (N=238)
Fussiness/Irritability (Any)	75.8% (N=1105)	70.7% (N=983)	67.1% (N=933)	54.4% (N=688)	34.9% (N=243)	22.9% (N=238)
Adapted from DAPTACEL® Prescribing Information, Tables 6 and 7.2 N ranges reflect the number of subjects for whom data were available for specific reactions/doses.
N/A: Not Assessed or Not Applicable for that dose.

• Postmarketing Experience: A variety of adverse events have been reported spontaneously during the postmarketing use of DAPTACEL®. These include lymphadenopathy; cyanosis; nausea, diarrhea; injection site reactions (such as pain, rash, nodule, mass, extensive swelling of the injected limb, cellulitis, abscess); hypersensitivity, allergic reaction, anaphylactic reaction (including edema, face edema, swelling face, pruritus, generalized rash), and other types of rash (erythematous, macular, maculopapular); nervous system disorders (convulsions including febrile, grand mal, and partial seizures, HHE, hypotonia, somnolence, syncope); and psychiatric disorders such as screaming.[2] Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

8. Drug Interactions

• Concomitant Vaccine Administration:
• DAPTACEL® can be administered concomitantly with other vaccines typically given during infancy and childhood. Studies have evaluated its co-administration with Haemophilus influenzae type b (Hib) conjugate vaccine, inactivated poliovirus vaccine (IPV), 7-valent pneumococcal conjugate vaccine (PCV7), hepatitis B vaccine, measles-mumps-rubella (MMR) vaccine, and varicella vaccine.[2]
• Generally, immune responses to the concomitantly administered vaccines were satisfactory. However, when DAPTACEL® was administered with the first dose of MMR vaccine, the mumps seroresponse rate was observed to be lower (86.6%) compared to when MMR was given non-concomitantly (90.1%). No interference was observed with measles, rubella, or varicella antigens, or with the fourth dose of PCV7.[2]
• Co-administration with Menactra® (Meningococcal (Groups A, C, Y, W) Conjugate Vaccine) has also been studied. When DAPTACEL® was given at the same time as Menactra®, antibody responses to the DAPTACEL® antigens (PT, FHA, PRN, tetanus, and diphtheria) were non-inferior to those observed when DAPTACEL® (and IPV) were administered separately. Anti-FIM geometric mean concentrations (GMCs) were marginally lower, though the clinical significance is unknown. A critical observation arises from the timing of administration: if DAPTACEL® (along with IPV) was administered 30 days prior to Menactra®, significantly lower serum bactericidal antibody (SBA-H) geometric mean titers (GMTs) to all four meningococcal serogroups (A, C, Y, W-135) were observed compared to when Menactra® was given alone or concomitantly.[2] This finding suggests a potential for immunological interference, where prior stimulation by DTaP components might negatively influence the response to subsequently administered meningococcal antigens. This underscores the necessity for healthcare providers to adhere strictly to recommended co-administration guidelines. Varying schedules without supportive data could lead to suboptimal protection against one or more diseases. This also highlights an area requiring further investigation to understand the mechanisms of such immunological interactions.
• Immunosuppressive Treatments: Individuals receiving immunosuppressive therapies (e.g., irradiation, antimetabolites, alkylating agents, cytotoxic drugs, or corticosteroids in doses greater than physiological) may have a diminished immune response to DAPTACEL®.[2]

9. Use in Specific Populations

• Pregnancy: DAPTACEL® is not indicated for use in pregnant women, as it is approved for children up to 6 years of age. Adacel® (Tdap) is the Sanofi Pasteur vaccine indicated for use during pregnancy.[3]
• Lactation: Not applicable for DAPTACEL®.
• Pediatric Use: DAPTACEL® is indicated for active immunization against diphtheria, tetanus, and pertussis as a five-dose series in infants and children 6 weeks through 6 years of age (prior to the 7th birthday). The safety and effectiveness of DAPTACEL® in infants younger than 6 weeks of age or in children 7 years of age and older have not been established.[2]
• Geriatric Use: Not applicable for DAPTACEL®.

10. Efficacy and Immunogenicity

• Diphtheria and Tetanus: In a US study, following the third dose of DAPTACEL®, 100% of children (N=1,099) achieved diphtheria antitoxin levels ≥0.01 IU/mL, and 98.5% achieved levels ≥0.10 IU/mL. After the fourth dose, 96.5% (N=659) achieved levels ≥1.0 IU/mL. For tetanus, after the third dose, 100% of children (N=1,037) achieved tetanus antitoxin levels ≥0.10 IU/mL. After the fourth dose, 98.8% (N=681) achieved levels ≥1.0 IU/mL.[2] These data indicate robust immunogenicity for the diphtheria and tetanus components.
• Pertussis:
• Sweden I Efficacy Trial: The efficacy of DAPTACEL® against pertussis was established in a large, randomized, double-blind, placebo-controlled trial conducted in Sweden. Infants received DAPTACEL® or a DT vaccine (control) at 2, 4, and 6 months of age. The protective efficacy of DAPTACEL® after three doses was 84.9% (95% CI: 80.1% to 88.6%) against pertussis defined by the World Health Organization (WHO) case definition (≥21 days of paroxysmal cough with confirmation of B. pertussis infection). Efficacy against mild pertussis (≥1 day of cough with confirmation) was 77.9% (95% CI: 72.6% to 82.2%). Protection was shown to be sustained during a 2-year follow-up period.[2]
• US Bridging Study: Immune responses to pertussis antigens following three doses of DAPTACEL® in US infants were compared to those in Swedish infants from the efficacy trial. Responses were generally similar, except for the PRN component, for which GMCs were significantly lower in US infants. Nevertheless, post-vaccination GMCs for all pertussis antigens in US infants were within the range of those observed in Swedish infants.[2]
• North American Studies (4 doses): Antibody responses to each of the pertussis antigens following the fourth dose of DAPTACEL® in North American infants were shown to be at least as high as those observed in Swedish infants after three doses (the regimen for which efficacy was demonstrated). While a serologic correlate of protection for pertussis has not been definitively established, the comparable or higher antibody responses after four doses in North American infants support the expectation of protection.[2]
• Concomitantly Administered Vaccines: As detailed in the Drug Interactions section, DAPTACEL® generally elicits satisfactory immune responses when co-administered with other routine pediatric vaccines, though specific nuances like the mumps response with MMR and interactions with Menactra® timing should be noted.[2] For example, when given with Hib conjugate vaccine, one month after the third dose, 96.9% of infants achieved anti-PRP antibody levels ≥0.15 mcg/mL and 82.7% achieved ≥1.0 mcg/mL. When co-administered with IPV, PCV7, and hepatitis B vaccine, at 7 months of age, 100.0% of subjects had protective neutralizing antibody levels for poliovirus types 1, 2, and 3; and 92.4% achieved anti-hepatitis B surface antigen levels ≥10.0 mIU/mL. For pneumococcal serotypes in PCV7, 91.3%-98.9% achieved anti-pneumococcal polysaccharide levels ≥0.5 mcg/mL for six of the seven serotypes, and 80.7% for serotype 6B.[2]

11. Storage and Handling

DAPTACEL® should be stored refrigerated at 2∘C to 8∘C (36∘F to 46∘F). It must not be frozen. If the vaccine has been frozen, it should be discarded. Before use, the vial should be shaken well to obtain a uniform, cloudy, white suspension. These are standard storage and handling procedures for most adsorbed vaccines to maintain their potency and safety, similar to those specified for other Sanofi Pasteur vaccines like Quadracel® [1] and Tenivac®.[8]

B. Adacel® (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed)

1. Composition and Formulation

Each 0.5 mL dose of Adacel® contains 5 Lf of tetanus toxoid, 2 Lf of diphtheria toxoid, and acellular pertussis antigens. The pertussis antigens consist of 2.5 µg of detoxified pertussis toxin (PT), 5 µg of filamentous hemagglutinin (FHA), 3 µg of pertactin (PRN), and 5 µg of fimbriae types 2 and 3 (FIM).[5] The quantities of diphtheria toxoid and detoxified PT are lower in Adacel® compared to DTaP vaccines like DAPTACEL®, which is characteristic of Tdap formulations intended for older individuals.

Other ingredients per 0.5 mL dose include 1.5 mg of aluminum phosphate (0.33 mg aluminum) as an adjuvant, ≤5 µg of residual formaldehyde, <50 ng of residual glutaraldehyde, and 3.3 mg (0.6% v/v) of 2-phenoxyethanol (not as a preservative).5

2. Indications and Usage

Adacel® is a vaccine indicated for:

• Active booster immunization against tetanus, diphtheria, and pertussis. Adacel® is approved for use in persons 10 through 64 years of age.[3]
• Immunization during the third trimester of pregnancy to prevent pertussis in infants younger than 2 months of age.[3]

3. Dosage and Administration

Adacel® is administered as a single 0.5 mL intramuscular injection.[3]

• Routine Booster Vaccination: A first dose of Adacel® is administered 5 years or more after the last dose of a Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) series or 5 years or more after vaccination with Tetanus and Diphtheria Toxoids Adsorbed (Td). A second dose of Adacel® may be administered 8 years or more after the first Tdap dose.[3]
• Immunization During Pregnancy: To provide protection against pertussis in infants younger than 2 months of age, Adacel® should be administered to pregnant individuals during the third trimester of pregnancy.[3] The FDA has approved both Adacel® and Boostrix® (another Tdap vaccine) for use during pregnancy.[5]
• Wound Management: Adacel® may be administered for tetanus prophylaxis for wound management. For a tetanus-prone wound, a booster dose of Adacel® may be given if at least 5 years have elapsed since the previous receipt of a tetanus toxoid-containing vaccine.[3]

Adacel® is supplied as a suspension for injection in single-dose vials and prefilled syringes.3

4. Mechanism of Action

• Tetanus: Induces neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level ≥0.01 IU/mL (neutralization assay) is considered the minimum protective level.[3]
• Diphtheria: Induces neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level providing some protection; ≥0.1 IU/mL is generally considered protective; 1.0 IU/mL is associated with long-term protection.[3]
• Pertussis: Induces an immune response to B. pertussis antigens. The exact correlates of protection are not clearly defined.[3]

5. Contraindications

Adacel® is contraindicated in individuals with:

• A history of a severe allergic reaction (e.g., anaphylaxis) to any component of Adacel® or to any other diphtheria toxoid, tetanus toxoid, or pertussis antigen-containing vaccine.[3]
• A history of encephalopathy (e.g., coma, prolonged seizures, or decreased level of consciousness) within 7 days of a previous dose of a pertussis-containing vaccine, not attributable to another identifiable cause.[3]

6. Warnings and Precautions

• Management of Acute Allergic Reactions: Epinephrine hydrochloride solution (1:1,000) must be available.[3]
• Guillain-Barré Syndrome (GBS) and Brachial Neuritis: If GBS occurred within 6 weeks of a prior tetanus toxoid-containing vaccine, there may be an increased risk for GBS following Adacel®. Tetanus toxoid has been causally linked to brachial neuritis.[3]
• Progressive or Unstable Neurologic Disorders: These are reasons to defer Adacel® vaccination. Administering Adacel® to individuals with such conditions could lead to diagnostic confusion or potentially hasten manifestations.[3]
• Arthus-Type Hypersensitivity: Persons who experienced an Arthus-type hypersensitivity reaction (a severe local reaction, Type III hypersensitivity) following a prior dose of a tetanus toxoid-containing vaccine should not receive Adacel® unless at least 10 years have elapsed since the last dose of a tetanus toxoid-containing vaccine.[3] This precaution is important because Arthus reactions are associated with high pre-existing levels of tetanus antitoxin. Waiting 10 years allows these antibody levels to wane, reducing the risk of such a reaction upon subsequent vaccination. This consideration is particularly relevant for Tdap and Td boosters, which are administered multiple times throughout an individual's life to maintain immunity.
• Altered Immunocompetence: The immune response may be diminished in immunocompromised individuals.[3]
• Syncope (Fainting): Can occur with injectable vaccines; procedures to prevent injury should be in place.[3]

7. Adverse Reactions

• Following the first vaccination with Adacel® (0-14 days post-vaccination):
• Adolescents (11-17 years): Most common solicited reactions were injection site pain (77.8%), headache (43.7%), body ache/muscle weakness (30.4%), tiredness (30.2%), injection site swelling (20.9%), and injection site erythema (20.8%). Fever (≥38.0∘C) occurred in 5.0%.[3]
• Adults (18-64 years): Most common solicited reactions were injection site pain (65.7%), headache (33.9%), body ache/muscle weakness (21.9%), tiredness (24.3%), injection site swelling (21.0%), and injection site erythema (24.7%). Fever (≥38.0∘C) occurred in 1.4%.[3]
• Following a second vaccination with Adacel® (0-7 days post-vaccination) in Adults (18-64 years):
• Most common solicited reactions were injection site pain (87.1%), myalgia (58.1%), headache (41.4%), malaise (33.3%), injection site swelling (6.9%), and injection site erythema (6.4%).[3]
• Postmarketing Experience: Spontaneously reported events include anaphylactic reaction, hypersensitivity reactions (angioedema, edema, rash, hypotension), paresthesia, hypoesthesia, GBS, brachial neuritis, facial palsy, convulsion, syncope, myelitis, myocarditis, pruritus, urticaria, myositis, muscle spasm, large injection site reactions (>50 mm), extensive limb swelling, injection site bruising/nodule, sterile abscess, and Arthus hypersensitivity.[3]

8. Drug Interactions

• Concomitant Vaccine Administration: Adacel® may be administered concomitantly with trivalent inactivated influenza vaccine (TIV) and with hepatitis B vaccine in persons 11 through 12 years of age. Studies showed no clinically significant interference with immune responses to these vaccines or to Adacel® antigens when co-administered.[3]
• Immunosuppressive Treatments: May reduce the immune response to Adacel®.[3]

9. Use in Specific Populations

• Pregnancy: Adacel® is indicated for immunization during the third trimester of pregnancy to prevent pertussis in infants younger than 2 months of age.[3] Observational studies have demonstrated the effectiveness of maternal Tdap vaccination in preventing infant pertussis. One such study estimated vaccine effectiveness at 88.0% (95% CI: 43.8, 97.4) when Adacel® was given during the third trimester and ≥14 days before delivery.[3]

However, a notable consideration is the potential impact of maternal Tdap vaccination on the infant's own immune responses to their primary DTaP vaccination series. Transplacentally transferred maternal antibodies, while protective for the young infant, can interfere with the infant's ability to mount their own robust immune response to DTaP antigens, a phenomenon known as "blunting." Published studies have reported diminished immune responses to pertussis antigens in DTaP-containing vaccines administered to infants whose mothers received Adacel® during the third trimester of pregnancy.3 The clinical significance of this blunting effect on the long-term effectiveness of the infant DTaP series is currently unknown and is an area of ongoing research and surveillance. This highlights a complex interplay between providing immediate passive protection to the vulnerable neonate and ensuring optimal long-term active immunity for the infant.

• Lactation: It is not known whether Adacel® antigens or antibodies are excreted in human milk. Data are not available to assess the effects of Adacel® on the breastfed infant or on milk production/excretion.[3]
• Pediatric Use: Safety and effectiveness of Adacel® in children younger than 10 years of age or older than 64 years of age have not been established, except for the pregnancy indication.[3]
• Geriatric Use: Clinical studies of Adacel® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.[3]

10. Efficacy and Immunogenicity

• Effectiveness of Tetanus and Diphtheria Toxoids: Based on immune responses compared to a US-licensed Td vaccine, with primary measures being the percentage achieving antibody levels ≥0.1 IU/mL.[3]
• Effectiveness of Pertussis Antigens: Evaluated by comparing pertussis antibody levels in Adacel® recipients to those in infants after DAPTACEL® vaccination, for which efficacy against pertussis was demonstrated.[3]
• Booster Response: Adacel® demonstrated an ability to elicit booster responses to tetanus, diphtheria, and pertussis antigens.
• First Vaccination (Adolescents and Adults 11-64 years): Anti-tetanus and anti-diphtheria seroprotection rates (≥0.1 IU/mL) and booster response rates were comparable to Td vaccine. Adacel® induced pertussis antibody levels non-inferior to those in Swedish infants after three doses of DAPTACEL®, and acceptable booster responses to each pertussis antigen were shown.[3]
• Second Vaccination (Adults 18-64 years, 8-12 years after initial Adacel®): Post-vaccination anti-pertussis GMCs were non-inferior to GMCs induced by DAPTACEL® in historical infant studies for PT, FHA, PRN, and FIM. Booster response rates for PT and FHA were non-inferior, but non-inferiority was not met for PRN and FIM booster response rates.[3]
• Immunization During Pregnancy: As noted above, maternal immunization with Adacel® is effective in preventing pertussis in young infants.[3]

11. Storage and Handling

Adacel® should be stored refrigerated at 2∘C to 8∘C (36∘F to 46∘F). It should not be frozen; if frozen, the vaccine must be discarded. The vial or syringe should be shaken well before use to obtain a uniform, cloudy suspension.[3]

C. Pentacel® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine)

1. Composition and Formulation

Each 0.5 mL dose of Pentacel®, after reconstitution, contains:

• DTaP components: 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, and acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg PRN, 5 µg FIM).[5]
• IPV components: Inactivated polioviruses: Type 1 (Mahoney strain) 40 D-antigen Units (DU), Type 2 (MEF-1 strain) 8 DU, and Type 3 (Saukett strain) 32 DU.[5]
• Hib component: 10 µg of polyribosyl-ribitol-phosphate (PRP) capsular polysaccharide of Haemophilus influenzae type b, covalently bound to 20 µg of tetanus toxoid protein (PRP-T).[5]

Other ingredients include aluminum phosphate (1.5 mg, 0.33 mg aluminum) as adjuvant, polysorbate 80 (approx. 10 ppm), sucrose (42.5 mg), residual formaldehyde (≤5 µg), residual glutaraldehyde (<50 ng), residual bovine serum albumin (≤50 ng), and 2-phenoxyethanol (3.3 mg, 0.6% v/v, not as a preservative).5

Pentacel® is supplied as a liquid DTaP-IPV component and a lyophilized ActHIB® (Hib conjugate vaccine) component, which must be reconstituted prior to administration.10 This reconstitution step is a key logistical consideration. While combination vaccines like Pentacel® aim to simplify immunization by reducing the number of injections, the requirement for reconstitution introduces an additional procedural step for healthcare providers. This step must be performed carefully according to instructions to ensure the correct dosage and maintain vaccine integrity, as errors could potentially affect efficacy or lead to administration errors. Proper training and adherence to these preparation protocols are therefore essential to realize the full benefits of such advanced vaccine formulations.

2. Indications and Usage

Pentacel® is indicated for active immunization against diphtheria, tetanus, pertussis, poliomyelitis, and invasive disease due to Haemophilus influenzae type b. It is approved for use as a 4-dose series in children 6 weeks through 4 years of age (prior to the 5th birthday).[9]

3. Dosage and Administration

The immunization series for Pentacel® consists of four 0.5 mL intramuscular injections, administered at 2, 4, 6, and 15-18 months of age. The first dose may be given as early as 6 weeks of age.[10]

• Four doses of Pentacel® constitute a primary immunization course against pertussis.
• Three doses of Pentacel® constitute a primary immunization course against diphtheria, tetanus, H. influenzae type b invasive disease, and poliomyelitis; the fourth dose serves as a booster for these antigens.[10]

Pentacel® may be used as the fourth dose in the 5-dose DTaP series in children who have received a 3-dose series of VAXELIS®. It may also be used to complete the first 4 doses of the 5-dose DTaP series in infants and children who have received one or more doses of DAPTACEL® and are also scheduled to receive the other antigens of Pentacel®.10

The Advisory Committee on Immunization Practices (ACIP) recommends that the final dose in the 4-dose IPV series be administered at age ≥4 years. When Pentacel® is administered at 2, 4, 6, and 15-18 months, an additional booster dose of an IPV-containing vaccine should be administered at age 4-6 years, resulting in a 5-dose IPV series.10

Reconstitution: The DTaP-IPV liquid component is used to reconstitute the lyophilized ActHIB® vaccine component. The vial of DTaP-IPV component should be shaken, its entire contents withdrawn and injected into the vial of lyophilized ActHIB®. The vial should then be gently swirled until a cloudy, uniform, white to off-white suspension results. The reconstituted vaccine should be administered intramuscularly, preferably in the anterolateral aspect of the thigh or the deltoid muscle.10

4. Mechanism of Action

Pentacel® induces an immune response to each of its antigenic components: diphtheria toxoid, tetanus toxoid, acellular pertussis antigens (PT, FHA, PRN, FIM), inactivated polioviruses (Types 1, 2, and 3), and Hib polysaccharide-protein conjugate, leading to the production of specific antibodies. Serological correlates of protection are established for diphtheria, tetanus, poliomyelitis, and Hib disease.[10]

5. Contraindications

Pentacel® is contraindicated in children with:

• A history of severe allergic reaction (e.g., anaphylaxis) to a previous dose of Pentacel®, any ingredient of Pentacel®, or any other DTaP, tetanus toxoid, pertussis-containing, IPV, or Hib conjugate vaccine.[10]
• Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine not attributable to another identifiable cause.[10]
• A progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, until a treatment regimen has been established and the condition has stabilized.[10]

6. Warnings and Precautions

• Management of Acute Allergic Reactions: Epinephrine (1:1000) must be available.[10]
• Adverse Reactions Following Prior Pertussis Vaccination: Careful consideration of benefits and risks if a prior pertussis vaccine led to: fever ≥40.5∘C (≥105∘F), HHE, or persistent inconsolable crying ≥3 hours within 48 hours; or seizures within 3 days.[10]
• Guillain-Barré Syndrome (GBS): If GBS occurred within 6 weeks of a prior tetanus toxoid-containing vaccine, the decision to give Pentacel® should be based on careful risk-benefit assessment.[10]
• Limitations of Vaccine Effectiveness: May not protect all individuals.[10]
• Altered Immunocompetence: Immune response may be diminished.[10]
• Apnea in Premature Infants: Has been observed; consider medical status and risk/benefit.[10]
• Syncope: Can occur; procedures to prevent injury from fainting.[10]
• Interference with Laboratory Tests: Urine antigen detection for H. influenzae type b may not be reliable following Pentacel® administration.[10]

7. Adverse Reactions

The most common solicited local and systemic adverse reactions following any dose included injection site tenderness, injection site redness, injection site swelling, fever, fussiness/irritability, and crying. Rates of redness, swelling, and tenderness at the injection site, as well as fever, tended to increase with successive doses of the 4-dose series. Serious adverse events were monitored; a causal relationship to Pentacel® was rare.[10]

8. Drug Interactions

• Concomitant Vaccine Administration: Pentacel® has been studied for concomitant administration with other pediatric vaccines such as Hepatitis B vaccine, pneumococcal conjugate vaccine (PCV), MMR vaccine, and Varicella vaccine. Immune responses were generally not impaired, but specific product labeling should be consulted.[10]
• Immunosuppressive Treatments: May reduce immune response.[10]

9. Use in Specific Populations

• Pediatric Use: Indicated for children 6 weeks through 4 years of age. Safety and effectiveness in infants <6 weeks or children ≥5 years not established.[10]

10. Efficacy and Immunogenicity

The efficacy of the DTaP components of Pentacel® is inferred from studies with DAPTACEL®, which contains the same pertussis antigens (though in different amounts for PT and FHA). The IPV and Hib components have demonstrated high immunogenicity, leading to seroprotective antibody levels in a high percentage of vaccinated children after the primary series. Clinical studies have demonstrated that Pentacel® is immunogenic for all its components and non-inferior to separately administered DTaP, IPV, and Hib vaccines for most antigens.[10]

11. Storage and Handling

The DTaP-IPV liquid component and the lyophilized ActHIB® component should be stored refrigerated at 2∘C to 8∘C (36∘F to 46∘F). Do not freeze. The DTaP-IPV component should be protected from light. After reconstitution, Pentacel® should be administered immediately.[10]

D. Quadracel® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine)

1. Composition and Formulation

Each 0.5 mL dose of Quadracel® contains:

• DTaP components: 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, and acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg PRN, 5 µg FIM).[1] The pertussis antigen content is similar to Pentacel® and VAXELIS®, with higher amounts of PT and FHA compared to DAPTACEL®.
• IPV components: Inactivated polioviruses: Type 1 (Mahoney) 40 DU, Type 2 (MEF-1) 8 DU, and Type 3 (Saukett) 32 DU.[1]

Other ingredients include 1.5 mg aluminum phosphate (0.33 mg aluminum) as adjuvant, polysorbate 80 (approx. 10 ppm), ≤5 µg residual formaldehyde, <50 ng residual glutaraldehyde, ≤50 ng residual bovine serum albumin, and 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as a preservative).5 Quadracel® is supplied as a suspension for injection in single-dose vials.1

2. Indications and Usage

Quadracel® is a vaccine indicated for active immunization against diphtheria, tetanus, pertussis, and poliomyelitis. A single dose of Quadracel® is approved for use as a fifth dose in the DTaP vaccination series and as a fourth or fifth dose in the IPV vaccination series in children 4 through 6 years of age whose previous DTaP vaccine doses have been with Pentacel®, DAPTACEL®, and/or VAXELIS®.[1] The development of Quadracel® was aimed at condensing the final doses of both DTaP and IPV, thereby reducing the total number of injections required at the preschool visit.[1] This targeted approach to simplifying the vaccination schedule for children aged 4-6 years can enhance the vaccination experience and potentially improve compliance with preschool booster doses. Reducing the number of shots addresses a common parental concern and streamlines logistics for healthcare providers. The average wholesale price (AWP) of Quadracel® has also been noted as comparable to or less than the combined AWP of separate DTaP and IPOL final vaccinations, suggesting it may also be a cost-effective option.[1]

3. Dosage and Administration

A single 0.5 mL intramuscular injection of Quadracel® is administered, typically into the deltoid muscle of the upper arm. The vial must be shaken well before use until a uniform, white, cloudy suspension results. Quadracel® should not be combined through reconstitution or mixed with any other vaccine.[1]

4. Mechanism of Action

Quadracel® induces an immune response to diphtheria toxoid, tetanus toxoid, acellular pertussis antigens (PT, FHA, PRN, FIM), and inactivated polioviruses (Types 1, 2, and 3), leading to the production of specific antibodies. Serological correlates of protection are established for diphtheria, tetanus, and poliomyelitis. The effectiveness against pertussis is based on a comparison of immune responses to DAPTACEL®, as both vaccines contain the same pertussis antigens (though Quadracel® has higher PT and FHA content) manufactured by the same process.[11]

5. Contraindications

Quadracel® is contraindicated in individuals with:

• A history of severe allergic reaction (e.g., anaphylaxis) to any ingredient of Quadracel®, or following any diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, or inactivated poliovirus vaccine.[11]
• Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine not attributable to another identifiable cause.[11]
• A progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, until a treatment regimen has been established and the condition has stabilized.[11]

6. Warnings and Precautions

• Management of Acute Allergic Reactions: Epinephrine (1:1000) must be available.[11]
• Adverse Reactions Following Prior Pertussis Vaccination: Careful risk-benefit assessment if a prior pertussis vaccine led to: fever ≥40.5∘C (≥105∘F), HHE, or persistent inconsolable crying ≥3 hours within 48 hours; or seizures within 3 days.[11]
• Guillain-Barré Syndrome (GBS): If GBS occurred within 6 weeks of a prior tetanus toxoid-containing vaccine, the decision to give Quadracel® should be based on careful risk-benefit assessment.[11]
• Limitations of Vaccine Effectiveness: May not protect all individuals.[11]
• Altered Immunocompetence: Immune response may be diminished.[11]
• Syncope: Can occur; procedures to prevent injury from fainting.[11]

7. Adverse Reactions

• Clinical Study Experience (Solicited Reactions): In a clinical study (Study M5I02), the most common solicited injection site reactions were pain (>75%), increase in arm circumference (>65%), erythema (>55%), and swelling (>40%). Extensive limb swelling occurred in 1.5%. Common solicited systemic reactions were myalgia (>50%), malaise (>35%), headache (>15%), and fever (6.0% any fever, 1.3% ≥39.0∘C).[11]
• Serious Adverse Events (SAEs): In Study M5I02, within 28 days post-vaccination, 0.1% of Quadracel® recipients experienced an SAE. Within 6 months, SAEs were reported in 0.8%, none assessed as vaccine-related.[11]
• Postmarketing Experience (outside US): Events reported include anaphylactic reaction, hypersensitivity, screaming, somnolence, convulsion, febrile convulsion, HHE, hypotonia, cyanosis, pallor, listlessness, injection site reactions (inflammation, mass, sterile abscess, edema), large injection site reactions, injection site cellulitis/abscess.[11]

8. Drug Interactions

• Concomitant Vaccine Administration: Quadracel® was studied for co-administration with MMR and Varicella vaccines. Immune responses to MMR and Varicella antigens were generally similar when given with Quadracel® compared to DAPTACEL® + IPOL. Responses to Quadracel® antigens were not adversely affected by co-administration.[11]
• Immunosuppressive Treatments: May reduce immune response.[11]

9. Use in Specific Populations

• Pediatric Use: Indicated for children 4 through 6 years of age for the specified booster doses. Safety and effectiveness in other age groups not established.[11]

10. Efficacy and Immunogenicity

Immunogenicity was evaluated in Study M5I02. Quadracel® was shown to be non-inferior to DAPTACEL® + IPOL vaccines (administered concomitantly at separate sites) based on post-vaccination antibody booster response rates and GMCs/GMTs for diphtheria, tetanus, all four pertussis antigens (PT, FHA, PRN, FIM), and poliovirus types 1, 2, and 3. For example, post-vaccination, 100.0% of Quadracel® recipients had anti-diphtheria and anti-tetanus antibody levels ≥0.1 IU/mL, and anti-poliovirus neutralizing antibody titers ≥1:8 dilution for all three types.[11]

11. Storage and Handling

Quadracel® should be refrigerated and stored at 2∘C to 8∘C (35∘F to 46∘F). It must not be frozen, as freezing destroys the vaccine. The expiration date on the label should always be checked before administration.[1]

E. Tenivac® (Tetanus and Diphtheria Toxoids Adsorbed)

1. Composition and Formulation

Each 0.5 mL dose of Tenivac® contains 5 Lf of tetanus toxoid and 2 Lf of diphtheria toxoid.[5] This formulation contains a reduced amount of diphtheria toxoid compared to pediatric DTaP or DT vaccines, making it suitable for older children and adults. The toxoids are adsorbed on aluminum phosphate (1.5 mg, providing

0.33 mg aluminum per dose) as an adjuvant.[5] The vaccine also contains

≤5.0 µg of residual formaldehyde.[5] Tenivac® is supplied as a sterile isotonic suspension in prefilled syringes or vials.[8]

A specific precaution for Tenivac® relates to its packaging: the tip caps of the Tenivac® prefilled syringes may contain natural rubber latex.4 This is an important consideration as natural rubber latex can cause allergic reactions in latex-sensitive individuals, ranging from mild local reactions to severe systemic anaphylaxis. Healthcare providers must therefore screen patients for latex allergy before administering Tenivac® from these prefilled syringes. If a patient has a known latex allergy, alternative vaccine presentations (e.g., vials, if confirmed to be latex-free) or different Td vaccine products that do not have latex-containing components in contact with the vaccine solution should be considered. This highlights the necessity of evaluating all aspects of a medicinal product, including its delivery system and packaging, to ensure patient safety.

2. Indications and Usage

Tenivac® is indicated for active immunization for the prevention of tetanus and diphtheria in persons 7 years of age and older.[4] Its uses include:

• Primary Immunization: For individuals not previously immunized against tetanus and diphtheria.[4]
• Routine Booster Immunization: Recommended for children 11-12 years of age and every 10 years thereafter.[4]
• Diphtheria Prophylaxis for Case Contacts: For post-exposure prophylaxis in certain situations.[4]
• Tetanus Prophylaxis in Wound Management: Preferred over single-antigen tetanus toxoid to enhance diphtheria protection.[4]

3. Dosage and Administration

• Primary Immunization: Three 0.5 mL doses. The first two doses are administered 2 months apart, and the third dose is given 6-8 months after the second dose.[4]
• Routine Booster/Other Uses: A single 0.5 mL dose as per specific recommendations (e.g., every 10 years for routine booster, or based on wound type and vaccination history for wound management).[4]

Tenivac® is administered intramuscularly, preferably into the deltoid muscle. The vial or syringe should be shaken well before use.4

4. Mechanism of Action

• Tetanus: Induces neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level ≥0.01 IU/mL (neutralization assay) or ≥0.1 IU/mL (ELISA) is considered protective.[4]
• Diphtheria: Induces neutralizing antibodies to diphtheria toxin. A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level providing some protection; ≥0.1 IU/mL is generally considered protective; 1.0 IU/mL is associated with long-term protection.[4]

5. Contraindications

Tenivac® is contraindicated in individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to a previous dose of Tenivac®, any other tetanus or diphtheria toxoid-containing vaccine, or any component of Tenivac®.[4]

6. Warnings and Precautions

• Management of Acute Allergic Reactions: Epinephrine (1:1000) must be available.[4]
• Latex: Tip caps of prefilled syringes may contain natural rubber latex.[4]
• Frequency of Administration: More frequent administration than recommended may increase adverse reaction incidence and severity.[4]
• Arthus Reactions: Persons with a history of Arthus-type hypersensitivity following a prior tetanus toxoid-containing vaccine should not receive Tenivac® more frequently than every 10 years, even for wound management.[4] This is due to high pre-existing tetanus antitoxin levels in such individuals, which can lead to immune complex formation and severe local reactions if boosted too soon.
• Guillain-Barré Syndrome (GBS) and Brachial Neuritis: Tetanus toxoid has been causally linked to GBS and brachial neuritis. If GBS occurred within 6 weeks of a prior tetanus toxoid vaccine, careful risk-benefit assessment is needed.[4]
• Limitations of Vaccine Effectiveness: May not protect all individuals.[4]
• Altered Immunocompetence: Immune response may be diminished.[4]
• Syncope: Can occur; procedures to prevent injury.[4]

7. Adverse Reactions

• Clinical Trials Experience (0-3 days post-vaccination):
• Injection Site Reactions: Pain was the most frequent (78.3% in ages 11-59; 35.3% in age ≥60). Redness and swelling were also common.[4]
• Systemic Reactions: Headache was most frequent (e.g., 23.0% adolescents, 25.1% adults 19-59). Muscle weakness, malaise, and joint pain were also reported.[4]
• Fever was reported in 2.5-5.7% depending on age group.[4]
• Postmarketing Experience: Lymphadenopathy, allergic/anaphylactic reactions, paresthesia, dizziness, syncope, GBS, vomiting, myalgia, pain in extremities, injection site reactions (inflammation, mass, edema, etc.), fatigue, peripheral edema.[4]

8. Drug Interactions

• Concomitant Vaccine Administration: No specific data provided for Tenivac® in the snippets, but general principles apply. If Tetanus Immune Globulin (Human) (TIG) is indicated for wound management, it should be given at a separate site with a separate needle/syringe.[4]
• Immunosuppressive Treatments: May reduce immune response.[4]

9. Use in Specific Populations

• Pregnancy: Pregnancy Registry data have not shown an increased risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes with Tenivac® exposure during pregnancy. Animal studies showed no adverse effects on fertility or fetal development.[4]
• Lactation: Data not available to assess effects on breastfed infant or milk production.[4]
• Pediatric Use: Indicated for persons ≥7 years. Not for children <7 years.[4]
• Geriatric Use: Participants ≥65 years had lower pre-vaccination seroprotective antibody levels and marginally lower post-vaccination responses for tetanus and diphtheria compared to younger adults, but adverse reaction rates were generally not higher.[4]

10. Efficacy and Immunogenicity

• Primary Immunization: A Canadian study showed that after a three-dose primary series, all 17 participants (ages 6-56) achieved protective antibody levels for both tetanus (>0.1 IU/mL) and diphtheria (>0.1 IU/mL).[4]
• Booster Immunization: In a US multicenter study, Tenivac® elicited robust booster responses for both tetanus and diphtheria antitoxins across adolescents (11-18 years), adults (19-59 years), and older adults (≥60 years). Post-vaccination, high percentages achieved seroprotective levels (e.g., for tetanus ≥0.1 IU/mL: 100% in adolescents and adults 19-59, 96.1% in adults ≥60; for diphtheria ≥0.01 IU/mL: 100% in adolescents, 99.2% in adults 19-59, 88.0% in adults ≥60).[4]

11. Storage and Handling

Tenivac® should be stored refrigerated at 2∘C to 8∘C (36∘F to 46∘F). It should not be frozen; discard if frozen. Protect from light.[8]

F. Vaxelis® (Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus b Conjugate and Hepatitis B Vaccine)

1. Composition and Formulation

Each 0.5 mL dose of Vaxelis® contains:

• DTaP components: 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, and acellular pertussis antigens (20 µg detoxified PT, 20 µg FHA, 3 µg PRN, 5 µg FIM).[5] The pertussis antigen content is similar to Pentacel® and Quadracel®.
• IPV components: Inactivated polioviruses: Type 1 (Mahoney) 29 DU, Type 2 (MEF-1) 7 DU, and Type 3 (Saukett) 26 DU.[5]
• Hib component: 3 µg of PRP of H. influenzae type b covalently bound to 50 µg of outer membrane protein complex of Neisseria meningitidis serogroup B (PRP-OMPC).[5]
• Hepatitis B component: 10 µg of Hepatitis B surface antigen (HBsAg).[5]

Vaxelis® is manufactured and marketed by MCM Vaccine Company, a partnership between Sanofi Pasteur and Merck.5

2. Indications and Usage

Vaxelis® is a vaccine indicated for active immunization to prevent diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B, and invasive disease due to Haemophilus influenzae type b (Hib). It is approved for use as a 3-dose series in children 6 weeks through 4 years of age (prior to the 5th birthday).[7] One of the key advantages highlighted for Vaxelis® is the reduction in the number of injections required during the infant vaccination series.[7]

3. Dosage and Administration

Vaxelis® is administered as a 3-dose series at 2, 4, and 6 months of age. The first dose may be given as early as 6 weeks of age.[12]

A critical point regarding the Vaxelis® schedule is that a 3-dose series does not constitute a primary immunization series against pertussis. An additional (fourth) dose of a pertussis-containing vaccine (e.g., Pentacel®, Quadracel®, or DAPTACEL®) is needed to complete the primary pertussis vaccination series.12 This is a significant scheduling and counseling consideration for healthcare providers. While Vaxelis® simplifies the initial phase of the infant immunization schedule by combining six antigens into fewer shots, meticulous tracking and ensuring the administration of the subsequent required pertussis dose are essential to prevent suboptimal protection against pertussis. This underscores that the benefits of highly combined vaccines must be balanced with a clear understanding of their specific contributions to the full immunization course for each antigen.

Vaxelis® may be used to complete the hepatitis B immunization series. It can also be used to complete the first 3 doses of the 5-dose DTaP series in infants who have received 1 or 2 doses of Pentacel® or DAPTACEL® and are also scheduled for the other antigens in Vaxelis®.12

4. Mechanism of Action

Vaxelis® induces an immune response to each of its six antigenic components.

• Diphtheria, Tetanus, Poliomyelitis, Hepatitis B, Hib Invasive Disease: Serological correlates of protection exist for these diseases. For diphtheria, antitoxin levels ≥0.1 IU/mL are generally protective. For tetanus, antitoxin levels ≥0.01 IU/mL (neutralization) or ≥0.1 IU/mL (ELISA) are protective. For poliomyelitis, type-specific neutralizing antibodies correlate with protection. For Hepatitis B, anti-HBsAg antibody concentrations ≥10 mIU/mL correlate with protection. For Hib, an anti-PRP level ≥0.15 mcg/mL is a minimal protective level, and ≥1.0 mcg/mL predicts longer-term protection.[12]
• Pertussis: Effectiveness against pertussis is based on immune responses following 3 doses of Vaxelis® compared to 3 doses of Pentacel®, and responses after a subsequent DTaP-containing vaccine dose.[12]

5. Contraindications

Do not administer Vaxelis® to individuals with:

• A history of severe allergic reaction (e.g., anaphylaxis) to a previous dose of Vaxelis®, any ingredient of Vaxelis®, or any other DTaP, tetanus toxoid, pertussis-containing, IPV, hepatitis B, or Hib vaccine.[12]
• Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous pertussis-containing vaccine, not attributable to another identifiable cause.[12]
• Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy, until a treatment regimen has been established and the condition has stabilized.[12]

6. Warnings and Precautions

• Management of Acute Allergic Reactions: Epinephrine (1:1000) must be available.[12]
• Adverse Reactions Following Prior Pertussis Vaccination: Careful risk-benefit assessment if prior pertussis vaccine led to: fever ≥40.5∘C (≥105∘F), HHE, persistent inconsolable crying ≥3 hours within 48 hours; or seizures within 3 days.[12]
• Guillain-Barré Syndrome (GBS) and Brachial Neuritis: Risk for GBS may be increased if it occurred within 6 weeks of a prior tetanus toxoid vaccine.[12]
• Altered Immunocompetence: Immune response may be diminished.[12]
• Apnea in Premature Infants: Has been observed; consider medical status and risk/benefit.[12]
• Limitations of Vaccine Effectiveness: May not protect all individuals.[12]
• Interference with Laboratory Tests: Urine antigen detection for Hib may not be reliable post-vaccination.[12]

7. Adverse Reactions

The most common solicited adverse reactions (0-5 days post-vaccination) were irritability (≥55), crying (≥45), injection site pain (≥44), somnolence (≥40), injection site erythema (≥25), decreased appetite (≥23), fever ≥38.0∘C (≥19), injection site swelling (≥18), and vomiting (≥9).[12]

Non-fatal serious adverse events occurred in 2.0% of Vaxelis® recipients and 2.2% of control vaccine recipients within 30 days in clinical studies. Four Vaxelis® recipients (0.1%) had vaccine-related SAEs (pyrexia, apparent life-threatening event). Six deaths (0.2%) occurred in the Vaxelis® group and one (0.1%) in the control group in two US studies; none were assessed as vaccine-related.12

Postmarketing reports include hypersensitivity, anaphylactic reaction, extensive limb swelling, seizure, febrile seizure, and HHE.12

8. Drug Interactions

• Concomitant Vaccine Administration: Vaxelis® was studied for co-administration with PCV13 (pneumococcal 13-valent conjugate vaccine) and rotavirus vaccine. Non-inferiority criteria were met for GMCs to 12 of 13 PCV13 serotypes (except serotype 6B).[12]
• Immunosuppressive Treatments: May reduce immune response.[12]

9. Use in Specific Populations

• Pediatric Use: Indicated for children 6 weeks through 4 years. Safety and effectiveness in infants <6 weeks or children ≥5 years not established.[12]
• Use in American Indian and Alaska Native (AI/AN) Infants: Vaxelis® is noted as the CDC's only preferred Hib combination vaccine for AI/AN infants.[7] This preferential recommendation suggests that Vaxelis® may offer particular advantages, such as enhanced immunogenicity against Hib or benefits related to schedule adherence, for this population, which has historically experienced higher rates of invasive Hib disease. While the specific reasons for this preference are not detailed in the provided information, it points to tailored public health strategies aimed at addressing specific epidemiological risks and population needs.

10. Efficacy and Immunogenicity

Effectiveness is based on the immunogenicity of individual antigens compared to US-licensed vaccines.

• Diphtheria, Tetanus, Poliovirus, Hepatitis B, Hib: Vaxelis® was non-inferior to Pentacel® + RECOMBIVAX HB® for proportions of participants achieving seroprotective antibody levels for these antigens in clinical studies (Studies 005 and 006).[12]
• Pertussis: Non-inferiority criteria for pertussis vaccine response rates and GMCs (except FHA GMCs in one study) were met after 3 doses of Vaxelis® compared to Pentacel®. Non-inferiority for all pertussis antigens was met after a fourth dose of DAPTACEL® or Pentacel® at 15 months.[12]

11. Storage and Handling

Vaxelis® should be stored refrigerated at 2∘C to 8∘C (36∘F to 46∘F). It should not be frozen. Protect from light. The syringe should be shaken well before use to obtain a uniform, cloudy, white suspension.[12]

IV. Comparative Insights and Considerations

A. Antigen Content Variations and Implications

The portfolio of DTP-containing vaccines from Sanofi Pasteur exhibits deliberate variations in antigen content, particularly for diphtheria and pertussis components. DTaP vaccines intended for primary immunization of infants (e.g., DAPTACEL®, and the DTaP components of Pentacel®, Quadracel®, Vaxelis®) contain a standard amount of diphtheria toxoid. In contrast, Tdap (Adacel®) and Td (Tenivac®) vaccines, designed for adolescents and adults, contain a reduced quantity of diphtheria toxoid.[5] This reduction is a well-established practice to minimize reactogenicity in older individuals who typically have pre-existing immunity from childhood vaccinations.

Similarly, there are notable differences in the quantities of acellular pertussis antigens. DAPTACEL® contains 10 µg of detoxified PT and 5 µg of FHA per dose.[5] In contrast, Pentacel®, Quadracel®, and Vaxelis® contain higher amounts:

20 µg of detoxified PT and 20 µg of FHA, along with similar amounts of PRN and FIM as DAPTACEL®.[2] Adacel® (Tdap) contains

2.5 µg of detoxified PT and 5 µg of FHA, reflecting a reduction appropriate for a booster dose in primed individuals.[5]

These variations in antigen load are not arbitrary but reflect a careful balance between achieving robust immunogenicity and maintaining an acceptable safety profile. For primary immunization in immunologically naive infants, a certain antigen level is required to establish strong and durable immunity. For booster doses in older children, adolescents, and adults, who have already been primed, lower antigen quantities are often sufficient to stimulate immunological memory and boost antibody levels effectively. These lower antigen doses, especially for diphtheria and pertussis components in Tdap vaccines, are generally associated with lower rates of local and systemic reactions, which is crucial for the acceptance and uptake of adolescent and adult booster immunizations. Despite the quantitative differences in pertussis antigens among the pediatric DTaP-containing vaccines, regulatory authorities often permit interchangeability for completing a DTaP series under specific conditions (e.g., DAPTACEL® can be used in a series initiated with Pentacel® or VAXELIS® [2]). This suggests that the resulting immune responses are considered adequately protective. The tailored antigen content across Sanofi Pasteur's DTP vaccine range thus demonstrates a sophisticated approach to vaccine formulation, grounded in age-specific immunology and the ongoing need to optimize the benefit-risk profile for diverse populations and immunization scenarios.

B. Age-Specific Indications and Scheduling

Sanofi Pasteur's DTP vaccine portfolio is clearly structured to support a life-course approach to immunization, with specific products tailored for different age groups and their corresponding immunological needs. DTaP vaccines (DAPTACEL® and the DTaP components of Pentacel® and Vaxelis®) are indicated for the primary series in infants starting as early as 6 weeks of age and for early childhood boosters up to age 6 years.[2] Quadracel® is specifically positioned as a DTaP-IPV preschool booster for children aged 4-6 years.[1] For adolescents and adults (typically 10 or 11 years through 64 years), Tdap vaccines like Adacel® are recommended for routine booster doses to maintain protection, particularly against pertussis, and also for pregnant women to protect their newborns.[3] Td vaccines such as Tenivac® are used for routine tetanus and diphtheria boosters in individuals aged 7 years and older, and for wound management.[4]

This strategic alignment of vaccine products with age-specific indications facilitates the implementation of comprehensive national immunization programs. Protection against diphtheria, tetanus, and especially pertussis can wane over time, necessitating booster doses throughout life to maintain both individual and herd immunity. Sanofi Pasteur's range of products directly supports this life-course immunization strategy by providing formulations optimized for primary immunization in infancy, consolidation of doses in early childhood (e.g., Pentacel®, Vaxelis®), preschool boosters (e.g., Quadracel®, DAPTACEL®), adolescent boosters (Adacel®), adult boosters (Adacel®, Tenivac®), and protection of special populations, such as neonates via maternal vaccination with Adacel®. This comprehensive approach is critical for preventing disease outbreaks and reducing the overall burden of these vaccine-preventable diseases across all age groups.

C. Considerations for Combination Vaccines

The development and widespread use of combination vaccines, such as Pentacel®, Quadracel®, and Vaxelis®, represent a significant advancement in pediatric immunization. The primary benefit is the reduction in the number of injections a child receives during an immunization visit.[1] This can lead to improved parental satisfaction, reduced child distress, and potentially better compliance with the complex pediatric immunization schedule. By simplifying immunization visits, combination vaccines can also enhance the efficiency of healthcare delivery.

However, the use of these sophisticated formulations also brings specific challenges and considerations. Some combination vaccines, like Pentacel®, require a reconstitution step before administration, where a lyophilized component (e.g., ActHIB®) must be mixed with a liquid DTaP-IPV component.[10] This adds a procedural step that requires careful attention to detail by healthcare providers to ensure correct preparation and dosing.

Furthermore, it is essential to ensure that all individual antigen components within a combination vaccine elicit adequate and non-inferior immune responses compared to when the antigens are administered as separate vaccines or in simpler combinations. This is typically demonstrated through extensive clinical trials and immunobridging studies.[11] Healthcare providers also need to be aware of specific nuances, such as the Vaxelis® 3-dose series not constituting a complete primary series for pertussis, thus requiring an additional pertussis-containing vaccine dose.[12] Managing inventory for multiple complex combination vaccines and ensuring appropriate use according to specific indications and prior vaccination history can also add complexity for immunization programs.

The introduction of combination vaccines has a broader impact on immunization programs beyond just reducing the number of shots. While the benefits are substantial, programs must adapt in terms of provider education on correct storage, handling (especially for reconstituted products), and administration. Accurate record-keeping becomes even more crucial to track which antigens a child has received and to ensure completion of all necessary series. Continued post-marketing surveillance for vaccine adverse events also remains important. The evolution towards more comprehensive combination vaccines requires a holistic approach by immunization programs to fully leverage their advantages while meticulously managing potential complexities to ensure that no gaps in protection occur.

V. Conclusion

A. Summary of Sanofi Pasteur's Diphtheria, Tetanus, and Pertussis Vaccine Offerings

Sanofi Pasteur provides an extensive and diverse portfolio of vaccines designed to protect against diphtheria, tetanus, and pertussis. This range includes standalone DTaP (DAPTACEL®) for infant primary series and early childhood boosters; Tdap (Adacel®) for adolescent and adult boosters, including crucial use during pregnancy; Td (Tenivac®) for older children and adults; and several advanced DTaP-based combination vaccines (Pentacel®, Quadracel®, Vaxelis®) that incorporate antigens against other diseases like poliomyelitis, Haemophilus influenzae type b, and Hepatitis B. This portfolio reflects an ongoing commitment to vaccine innovation, aiming to enhance safety, improve immunogenicity, and simplify complex immunization schedules by reducing the number of injections, thereby supporting public health efforts to maintain high vaccination coverage across different age groups.

B. Reiteration of the Importance of These Vaccines in Public Health

Vaccination remains the most effective public health intervention for preventing diphtheria, tetanus, and pertussis. The widespread use of these vaccines has led to a dramatic reduction in the incidence, morbidity, and mortality associated with these once-common and devastating diseases. Continued adherence to recommended immunization schedules is critical for maintaining individual protection and robust herd immunity, thereby preventing resurgence and protecting vulnerable populations, including young infants who are not yet fully immunized. The success of these vaccines is a testament to their profound impact on global health.

C. Key Takeaways for Healthcare Providers

Healthcare providers play a central role in the successful implementation of DTP immunization programs. Several key takeaways emerge from this review of Sanofi Pasteur's vaccine portfolio:

1. Age-Appropriate Vaccine Selection: It is paramount to select the correct vaccine formulation (DTaP, Tdap, Td, or specific combination vaccine) based on the individual's age, vaccination history, and current immunization recommendations.
2. Awareness of Vaccine Characteristics: A thorough understanding of each vaccine's specific composition (including antigen quantities), indications, contraindications (e.g., severe allergy, encephalopathy), and potential warnings and precautions (such as history of Arthus reactions, GBS, or latex sensitivity for Tenivac® prefilled syringes) is essential for safe and effective administration.
3. Administration and Handling: Strict adherence to recommended administration routes (intramuscular), schedules, and specific handling instructions (e.g., reconstitution for Pentacel®, shaking before use, proper storage conditions) is crucial to ensure vaccine potency and safety.
4. Patient Counseling: Providers must effectively counsel patients and/or parents regarding the benefits of vaccination, the diseases prevented, common and expected adverse reactions, and the management of such reactions.
5. Combination Vaccine Nuances: When using combination vaccines, providers must be aware of their specific characteristics, such as the need for an additional pertussis dose to complete the primary series after Vaxelis® administration, or the particular role of Quadracel® in consolidating preschool booster doses.
6. Maternal Tdap Vaccination: Recognizing the importance of Tdap vaccination during pregnancy (e.g., with Adacel®) for protecting newborns from pertussis is critical, alongside understanding any potential implications for the infant's subsequent DTaP responses.
7. Interchangeability and Mixed Schedules: While some interchangeability is permitted (e.g., DAPTACEL® in a series started with Pentacel® or VAXELIS®), it is generally recommended to complete a series with the same product if possible, or to follow specific guidance when products are mixed. Data on mixed schedules with vaccines from different manufacturers are often limited.

By maintaining up-to-date knowledge of these vaccines and adhering to best practices, healthcare providers can continue to leverage these powerful tools to protect individuals and communities from diphtheria, tetanus, and pertussis.

Works cited

1. Quadracel: Vaccination Against Diphtheria, Tetanus, Pertussis, and Poliomyelitis in Children, accessed June 13, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC4811254/
2. Package Insert - DAPTACEL - FDA, accessed June 13, 2025, https://www.fda.gov/media/74035/download
3. Package Insert - Adacel - FDA, accessed June 13, 2025, https://www.fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Package-Insert-Adacel.pdf
4. Package Insert-TENIVAC - FDA, accessed June 13, 2025, https://www.fda.gov/media/76610/download
5. About Diphtheria, Tetanus, and Pertussis Vaccination | CDC, accessed June 13, 2025, https://www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/about-vaccine.html
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9. DTaP-IPV/ Hib Vaccination for Kids | Pentacel® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine) | Quadracel® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine) | Sanofi, accessed June 13, 2025, https://www.pentacel.com/
10. Package Insert – Pentacel - (inactivated poliovirus component ... - FDA, accessed June 13, 2025, https://www.fda.gov/media/74385/download
11. Package Insert - Quadracel (inactivated poliovirus component ... - FDA, accessed June 13, 2025, https://www.fda.gov/media/91640/download
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13. Tenivac (Tetanus and Diphtheria Toxoids Adsorbed): Side Effects, Uses, Dosage, Interactions, Warnings - RxList, accessed June 13, 2025, https://www.rxlist.com/tenivac-drug.htm