MedPath

Vaccine Hyporesponse in Healthy Elderly Participants (MK-0000-131 AM2)

Completed
Conditions
Vaccine Response Impaired
Interventions
Biological: Tetanus & Diphtheria booster vaccine (Td)
Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]
Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)
Registration Number
NCT01119703
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

This study evaluated whether it is possible in healthy elderly participants to generate baseline biomarker-based prediction rules (PdR) for vaccine response (post baseline absolute serum antibody titer) using each of the protocol selected vaccines separately; and examined the rank correlation coefficients of pairs of post vaccination antibody titers within the same elderly individuals.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
174
Inclusion Criteria
  • Male or female aged 25 to 40 years old or 65 years of age or older at the prestudy (screening) visit
  • Has no fever on day of screening
  • Lacks Hepatitis B surface antigen seroreactivity
  • If female 25 to 40 years of age, is not pregnant nor breastfeeding, and agrees to use effective contraception
Exclusion Criteria
  • Has a prior history of Hepatitis B Virus infection
  • Has BMI (Body Mass Index) >35
  • If female 25 to 40 years of age, is pregnant, or expecting to conceive, donate eggs or breastfeed
  • Has received immune globulin and/or blood products within 3 months prior to first dose received
  • Has a history of immunosuppression resulting from disease (e.g., malignancy; human immunodeficiency virus [HIV] infection), or is currently taking corticosteroids or other immunosuppressive/cytotoxic therapy (cancer chemotherapy or organ transplantation)
  • Has an active neoplastic disease
  • Has had any infection including upper respiratory viral syndrome in the 6 weeks prior to planned collection of baseline laboratory samples
  • Has received a live virus vaccine or an inactivated vaccine or is scheduled to receive a live virus vaccine or an inactivated vaccine in the period from 6 weeks prior to receipt of the first vaccine through the completion of all study visits

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Arm 1: Healthy, elderly participantsTwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]Healthy participants 65 years old and older.
Arm 2: Healthy, young, participantsDukoral® Traveler's Diarrhea Vaccine (WC/rBS)Healthy participants 25 to 40 years old.
Arm 1: Healthy, elderly participantsTetanus & Diphtheria booster vaccine (Td)Healthy participants 65 years old and older.
Arm 2: Healthy, young, participantsTetanus & Diphtheria booster vaccine (Td)Healthy participants 25 to 40 years old.
Arm 2: Healthy, young, participantsTwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]Healthy participants 25 to 40 years old.
Arm 1: Healthy, elderly participantsDukoral® Traveler's Diarrhea Vaccine (WC/rBS)Healthy participants 65 years old and older.
Primary Outcome Measures
NameTimeMethod
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.Baseline and 1 month after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.Baseline and 3 weeks after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.Baseline and 1 month after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.Baseline and 1 month after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.3 weeks or 1 month after each final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln).

Secondary Outcome Measures
NameTimeMethod
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.Day 7 and 1 month after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.Day 7 and 1 month after each final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.Day 7 and 1 month after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.Day 7 and 3 weeks after final vaccination

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

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