A Randomized Clinical Trial of an Inactivated Avian Influenza A (H7N7) Vaccine

Background: Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2). Objective: To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans. Design: One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 mu g of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months. Results: Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a >= 4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of >= 1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of >= 1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 mu g HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 mu g HA group developed a >= 4-fold rise in antibody in this test and only one of these achieved a titer of >= 1:32. Conclusion: This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.