Inactivated Influenza A/H5N1 Vaccine in the Elderly

The goals of this study are to compare the safety, reactogenicity, and immunogenicity of two dose levels of monovalent subvirion influenza A/H5N1 virus vaccine administered by injection to healthy elderly adults aged 65 years and older. Researchers hypothesize that a dose of either 45 micrograms or 90 micrograms of H5N1 vaccine will be well tolerated and result in acceptable immunogenicity. Thus, the primary goal of this study is to determine the lowest dose level of H5N1 that will result in an acceptable proportion of subjects achieving a potentially protective postvaccination antibody titer combined with an acceptable safety profile. The study will enroll at least 240 (and up to 260) healthy ambulatory male and female subjects aged 65 and older, in the United States, may be enrolled. Three doses of the vaccine at 2 dose levels (45 micrograms or 90 micrograms) or saline placebo will be administered 28 days apart for the first two doses. The third dose will be given six months after the first dose. Serum hemagglutination inhibition (HAI) and neutralizing antibody titers will be assessed approximately 1 month after receipt of each dose and 6 month after first and third doses. The primary objectives of the study are: to determine the dose-related safety of intramuscular (IM) subvirion inactivated H5N1 vaccine in healthy elderly adults (65 years of age and older); to determine the immunogenicity of IM subvirion inactivated H5N1 vaccine approximately 1 month following receipt of 2 doses of vaccine; and to provide information for the selection of the best dose level(s) for further studies. The secondary objective is to determine the immunogenicity of IM subvirion inactivated H5N1 vaccine approximately 1 and 6 months following receipt of first and third doses of the vaccine. The primary endpoints include: adverse event (AE) or serious adverse event (SAE) information (solicited in-clinic and via memory aids, concomitant medications, and periodic targeted physical assessments); proportion of subjects achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus 28 days after receipt of second dose of vaccine (approximately Day 56); geometric mean titer (GMT) and the frequency of 4-fold or greater increases in neutralizing antibody titers 28 days after receipt of second dose of vaccine (approximately Day 56). The secondary endpoints include: development of serum antibody responses against antigenically drifted variants of H5N1 influenza virus and geometric mean titer and the frequency of 4-fold or greater increases in serum hemagglutination inhibition (HAI) and neutralizing antibody titer 1 and 6 months after receipt of first and third dose of vaccine. The duration of the study will be approximately 15 months (approximately 14 months for each subject). This study is linked to DMID protocols 07-0022 and 05-0006.