The purpose of this research study is to compare how the body reacts to different strengths of an H5N1 flu vaccine when given by different routes of injection (injection into the skin or into the muscle). It will also compare how antibodies (proteins produced by the body's immune system that recognize and help fight infections and other foreign substances in the body) are made after receiving the H5N1 flu vaccine. Participants will include 100 healthy adults, ages 18-40 years. Study procedures include blood samples and completing a memory aid documenting daily oral temperature and side effects for 7 days following each vaccination. Participants may be involved in the study for up to 13 months.
This is a single-center, randomized, open-label, dose-ranging, phase I comparative trial of intradermal (ID) and intramuscular (IM) injection with subvirion inactivated influenza A/H5N1 vaccine in healthy adults, 18 to 40 years old, inclusive. This study is designed to investigate the safety, reactogenicity, and dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine given by ID injection compared to IM injection. The primary objectives of this study are to: compare dose-related safety and reactogenicity profiles of ID and IM injection with subvirion inactivated influenza A/H5N1 vaccine among healthy young adults; compare the dose-related immunogenicity of subvirion inactivated influenza A/H5N1 vaccine given by ID with vaccine given by IM injection among healthy young adults 1 month after receipt of the second dose of vaccine; and provide information for the selection of the best dose levels for further studies. The secondary objectives of this study are to: evaluate dose-related immunogenicity and the percent of subjects responding approximately 1 and 7 months after the first vaccination; and evaluate the dose-related safety, reactogenicity and immunogenicity following receipt of a third dose of vaccine administered 6-7 months after the second dose of vaccine. The study will have 2 comparison arms (IM and ID), and 2 dosage levels will be evaluated in each arm (4 vaccine groups total). Subjects will be randomized 1:1:1:1 (25 subjects in each group) to receive 2 doses 1 month apart of an inactivated influenza A/H5N1 vaccine containing 15 mcg or 45 mcg of H5 HA by the IM route; or one-fifth of the IM dose (3 mcg or 9 mcg) by the ID route. Subjects will maintain a memory aid recording oral temperature, and systemic and local adverse events for 7 days after each inoculation. Serum for immunogenicity evaluations will be obtained prior to first vaccination, at Day 0, prior to second vaccination, at Day 28, and on Day 56 and approximately Day 215 (7 months) after dose 1. This study is linked to DMID protocol 07-0022.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
100
Monovalent subvirion H5 vaccine (HA of A/Vietnam/1203/04), inactivated A/H5N1 vaccine administered intradermally (ID); doses: 3 or 9 micrograms.
Monovalent subvirion H5 vaccine (HA of A/Vietnam/1203/04), inactivated A/H5N1 vaccine administered intramuscularly (IM); doses: 15 or 45 micrograms.
Baylor College of Medicine
Houston, Texas, United States
Proportion of subjects in each vaccine group achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus.
Time frame: Day 56.
Geometric mean titer (GMT) and proportion of subjects achieving a 4-fold or greater increase in serum neutralizing or hemagglutination inhibition (HAI) antibody titer in each group.
Time frame: Day 56.
Adverse event (AE) or serious adverse event (SAE) information (solicited in-clinic and via memory aids and periodic targeted physical assessments).
Time frame: Duration of study.
Geometric mean titer (GMT) and proportion of subjects achieving a 4-fold or greater increase in neutralizing antibody titers in each group 1 and 7 months after receipt of dose 1.
Time frame: Blood samples for serum assays will be collected prior to first dose on day 0, prior to second dose on day 28, and on days 56 and 215 after the first immunization.
GMT and the proportion of subjects achieving a 4-fold or greater increase in HAI and neutralizing antibody titers in each group 1 month after receipt of a 3rd dose of vaccine administered approximately 6-7 months after the 2nd dose of vaccine.
Time frame: Blood samples for serum assays will be collected prior to first dose on day 0, prior to second dose on day 28, and on days 56 and 215 after the first immunization.
Development of serum antibody responses against antigenically drifted variants of H5 influenza virus.
Time frame: Blood samples for serum assays will be collected prior to first dose on day 0, prior to second dose on day 28, and on days 56 and 215 after the first immunization.
Geometric mean titer (GMT) and proportion of subjects achieving a 4-fold or greater increase in HAI and neutralizing antibody titers in each group 1 and 7 months after receipt of dose 1.
Time frame: Blood samples for serum assays will be collected prior to first dose on day 0, prior to second dose on day 28, and on days 56 and 215 after the first immunization.
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