Immunogenicity and Safety PCV-20 of the Vaccine Administered During an Acute Febrile Illness in Adults
- Conditions
- Acute Febrile IllnessPneumococcal Infections
- Interventions
- Biological: Early interventionBiological: Delayed intervention
- Registration Number
- NCT06822907
- Brief Summary
Streptococcus pneumoniae is responsible for serious infections associated to numerous hospitalizations and high rate of mortality. The incidence and therefore the burden of pneumococcal infections have been significantly reduced thanks to the use of pneumococcal conjugate vaccines (PCVs). PCVs were shown to be effective against vaccine-type serotypes causing both non-invasive and invasive pneumococcal diseases (IPD) in children and adults. PCVs use in children was shown to have an impact on IPD incidence among adults due to herd immunity and on antimicrobial resistance. To increase the protection of at-risk patients against IPD, the 20-valent PCV (PCV-20) is recently recommended in adults, after a period where PCV-13 followed by pneumococcal polysaccharide vaccine 23 valent (PPV-23) was recommended. PCV-20 effectiveness against IPD and against pneumonia was inferred from immunobridging with PCV-13. Indeed PCV-13 was shown effective to reduce the incidence of low respiratory tract infections and IPD (bacteraemia and meningitis) in 65-years-old-adults and older. Currently immunization against S. pneumoniae is recommended with PCV-20 for adult patients at-risk for IPD such as immunocompromised (=high-risk patients) and in immunocompetent people with underlying chronic conditions (cardiovascular, liver, pulmonary, kidney diseases and diabetes mellitus) (=medium risk patients). However, vaccine coverage against IPD in adults remains low globally, and does not exceed 5 % in France. Reducing missed opportunities of vaccination for S. pneumoniae is crucial.
- Detailed Description
Patients at-risk of IPD are very frequently hospitalized for acute febrile illnesses. More than 50 % of the IPD at-risk patients hospitalized for an IPD or a pneumonia have been admitted to the hospital during the past 5 years without receiving a pneumococcal vaccination. Hospitalization appears to be therefore an opportunity to provide vaccines. However, physicians usually consider that vaccines should be postponed during an acute febrile illness including if non-severe. This consideration of not vaccinating during an acute febrile illness is however not evidence-based. This is associated to concerns about a potential risk of an impaired response to the vaccine and safety. In children, data about vaccination during a febrile illness have shown no safety nor efficacy concerns. In most countries, recommendations regarding this particular point are unclear.
In fine, vaccination is then rarely provided during the hospital stay as well as after discharge including in the USA, a country where it is recommended to vaccinate whatever the body temperature is and during hospitalization. Reluctance to immunize adults in this situation is probably due to the absence of evidence showing that it is as effective and safe as vaccinating patients without an acute or febrile illness.
To reduce the number of missed opportunities to immunize adults against S. pneumoniae, investigators aim to demonstrate that the administration of PCV-20 during an acute non-severe febrile illness is non-inferior than the administration one month after fever resolution in terms of immunogenicity (assessed by vaccine types (VT) Immunoglobulin G (IgG) concentrations and at least 2-fold change increase), and that it is as safe.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 1052
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Early vaccination Early intervention The patient will receive unique dose of the PCV-20 vaccine as soon as possible and until 72h after apyrexia. The "Prevenar 20" will be used Delayed vaccination Delayed intervention From 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature \< 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive PCV-20 vaccination The "Prevenar 20" will be used
- Primary Outcome Measures
Name Time Method Proportion of immune "good responders" to PCV-20 in both arms 1 month post vaccination Good responders is defined as - a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG \> 1,3 μg/mL in ≥ 10 out 13 VT.
OR
- -a seroconversion (a 4-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG \< 1,3 μg/mL in ≥ 10 out 13 VT.
- Secondary Outcome Measures
Name Time Method Safety endpoints in both arms in the month following vaccination : adverse events 1 month post vaccination Number, type and severity of solicited (in the 7 days following vaccination) and unsolicited (in the month following vaccination) adverse events
Frequency of local reactions 1 month post vaccination Local reactions will be defined as : pain, redness, and swelling at the study vaccine injection site and limitation of arm movement
Frequency of systemic events related to the vaccination 1 month post vaccination Onset or worsening of fever, diarrhoea, chills, fatigue, headache, vomiting, decreased appetite, rash, muscle pain, joint pain). An independent blinded central adjudication committee will define the onset or worsening of symptoms and will review all systemic events.
Proportion of immune good responders serotype by serotype 1 month post vaccination "Good responders" being defined above (primary end-point)
A blood sample for immunologic analysis will be performedopsonophagocytic activity (OPA) IgG titers for serotype by serotype 1 month post vaccination A blood sample for immunologic analysis will be performed. ELISA method will be used for immunologic analysis.
Proportion of the participants immune "good responders" to PCV-20 in both arms. 1 year post vaccination "Good responders" being defined above (primary end-point) A blood sample for immunologic analysis will be performed. ELISA method will be used for immunologic analysis.
Number of low respiratory tract infections events 1 year post vaccination Data about occurrence of respiratory infections will be recorded.
Number of confirmed S.pneumoniae infections 1 year post vaccination Data about pneumococcal infection will be recorded.
Analyze the gut microbiota on the immune response 1 year post vaccination Analyze the gut microbiota on the immune response in both arm ( during an acute febrile illness or 15-58 days after resolution of the acute febrile illness)
A stool sample is taken before vaccinationReactogenic inflammatory response after vaccination 1 month post vaccination Fold change kinetics (transcriptomics) (before and at 24 hours after vaccination) of vaccine-induced gene signatures in peripheral blood mononuclear cells and serum cytokine levels at baseline and 24 hours after vaccination in both arms.
Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells 1 year post vaccination Blood sample will be collected 1 year post-vaccination.
Frequency of specific PCV-20 interferon-gamma (IFNg) secreting CD4 or CD8 T cells 1 month post vaccination Blood sample will be collected 1 month post-vaccination.
Proportion of volunteers with circulatory immunoglobulin A (IgA) 1 month post vaccination Blood sample will be collected 1 month post-vaccination.
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Trial Locations
- Locations (10)
Centre Hospitalier
🇫🇷La Roche-sur-Yon, France
Centre Hospitalier Universitaire
🇫🇷Rouen, France
Centre Hospitalier General Metropole Savoie
🇫🇷Chambéry, France
Centre Hospitalier de Creteil
🇫🇷Créteil, France
Centre Hospitalier General
🇫🇷Le Mans, France
Hospices Civils de Lyon
🇫🇷Lyon, France
Centre Hospitalier Regional Universitaire
🇫🇷Montpellier, France
Centre Hospitalier Bichat
🇫🇷Paris, France
Assistance Publique Hopitaux de Paris
🇫🇷Paris, France
CHU de Saint-Etienne
🇫🇷Saint-etienne, France