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

A Phase I, Open-Label Observational Study to Develop a Prospective Predictor of Vaccine Hyporesponse in Healthy Elderly Subjects

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.

Study Overview

• Status: Completed
• Conditions: Vaccine Response Impaired
• Intervention / Treatment: Biological: Tetanus & Diphtheria booster vaccine (Td); Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]; Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)

• Study Type: Observational
• Enrollment (Actual): 174

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adults 25 to 40 years old or 65 years and older

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm 1: Healthy, elderly participants; Healthy participants 65 years old and older.	Biological: Tetanus & Diphtheria booster vaccine (Td); Tetanus & Diphtheria booster vaccine (Td), single intramuscular dose; Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]; TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine], intramuscular, two doses of standard three dose regimen (opposite arms); Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS); Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen
Arm 2: Healthy, young, participants; Healthy participants 25 to 40 years old.	Biological: Tetanus & Diphtheria booster vaccine (Td); Tetanus & Diphtheria booster vaccine (Td), single intramuscular dose; Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]; TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine], intramuscular, two doses of standard three dose regimen (opposite arms); Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS); Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Baseline and 1 month after final vaccination
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Baseline and 1 month after final vaccination
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Baseline and 1 month after final vaccination
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Baseline and 3 weeks after final vaccination
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.	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).	3 weeks or 1 month after each final vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	Day 7 and 1 month after final vaccination
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Day 7 and 1 month after each final vaccination
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Day 7 and 1 month after final vaccination
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.	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).	Day 7 and 3 weeks after final vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Francois St-Maurice, MD, Anapharm; Principal Investigator: Denis Audet, MD, Anapharm

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 5, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Estimate): December 29, 2015
• Last Update Submitted That Met QC Criteria: November 30, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Vaccine Hyporesponse
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 0000-131; MK-0000-131 (Other Identifier: Merck)