Cell-Mediated Immune Responses to Influenza A/H5N1 Vaccine

This study is linked to DMID protocol 04-063 and 04-076, "A Randomized, Double Blinded, Placebo-ontrolled, Phase I/II, Dose-Ranging Study of the Safety, Reactogenicity, and Immunogenicity of Intramuscular Inactivated Influenza A/H5N1 Vaccine in Healthy Adults (04-063)" and also "in Healthy Elderly Adults" (04-076). All adult subjects enrolled in the main vaccine trials at Vanderbilt (04-076), Maryland (04-063), and Rochester (04-063) will be eligible for enrollment in the cell-mediated immune response sub-study. A maximum of 232 healthy ambulatory male and female subjects; 180 subjects 18 to 64 years old and 64 subjects aged 65 years and older, in the United States, could be enrolled. The primary objectives are: to establish a reproducible, functional cell-mediated immune response assay to evaluate the magnitude and functional capacity of T cells responding to monovalent subvirion H5 influenza vaccine and to evaluate the percent of subjects demonstrating a CD4+ and/or CD8+ response approximately 14 days after the first vaccination and 14 days and 6 months after the second vaccination (04-063), and 14 days after the first and second vaccination and 14 days and 6 months after the third vaccination (04-076). The secondary objectives are: to evaluate dose-related and age-related humoral immunogenicity compared to the cellular immune responses approximately 14 days after the first vaccination and 14 days and 6 months after the second vaccination (04-063), and 14 days after the first and second vaccination and 14 days and 6 months after the third vaccination (04-076) and to establish CMI assays that can be applied to future avian vaccine immunogenicity evaluation, such as the Chiron H9N2 avian influenza vaccine, future H7 vaccines, or vaccines with other avian HA molecules. The study outcome measure, immunogenicity will be based on H5 strain-specific cell-mediated immunity measured 14 days after the first, second, and third (04-076 only) dose, and month 6 after the last dose of vaccine.

Inclusion criteria

• All subjects who are eligible and enrolled in the main monovalent subvirion H5 vaccine trials [Division of Microbiology and Infectious Diseases (DMID) studies 04-063 and 04-076] and have agreed to the extra blood draws for the cell-mediated immunity (CMI) sub-study will be enrolled.
• Subjects will not be recruited outside the main vaccine trials or future DMID sponsored influenza A/H5N1 studies.
• Subjects who understand and sign the consent form for this study.
• Subjects who meet pre-screening qualifications for the DMID study will be eligible for the initial pre-vaccination blood draw.
• Subjects who meet all inclusion criteria for the DMID study and who are vaccinated will be allowed to participate in the remaining portions of this study.

Exclusion criteria

• All subjects who are ineligible for the main monovalent subvirion H5 vaccine trials will not be eligible for the cell-mediated immunity (CMI) sub-study.