Prevention of influenza by the intranasal administration of cold-recombinant, live-attenuated influenza virus vaccine: importance of interferon-γ production and local IgA response

Abstract

To clarify which immunological factors were more effective in preventing influenza virus infection, we measured immunological parameters induced by vaccination and infection in vivo and in vitro. Healthy adult subjects (n = 128) were divided into vaccinated (n = 85) and untreated (n = 43) groups. Eighty-five were vaccinated intranasally with a trivalent cold-adapted recombinant influenza virus vaccine containing type A (H1N1 and H3N2) and B viruses. Subjects were mostly seropositive before vaccination. In 29 (80.6%) of the 36 examinees showing a prevaccination HI antibody titre of less than 1:128, the titre increased more than four times after vaccination. On the other hand, an increase of more than four times was found in four (8.2%) of the 49 individuals who had shown a prevaccination titre of more than 1:128. The IgA antibody was negligibly detected in the nasal wash specimens before vaccination, and was induced by vaccination in some cases. Lymphocyte proliferation and interleukin 2 (IL-2) production in cultured lymphocytes of the same subjects stimulated by H1N1 virus in vitro were correlated with the HI antibody titre. However, the interferon γ (IFN-γ) production was low before vaccination, regardless of the HI antibody titre, and showed a significant increase after vaccination. It was suggested that local IgA response and IFN-γ production play important roles in the prevention of influenza. Since there was the outbreak of influenza A (H1N1) in Kochi Prefecture after completion of blood samples 6–8 weeks after the second vaccination, we examined the above hypothesis. A significantly (p<0.01) lower morbidity rate in the vaccinated examinees was found. The HI antibody, lymphocyte DNA synthesis and IL-2 production, which had been increased by vaccination, showed little further increase in response to the epidemic. In contrast, local IgA response and IFN-γ production, which had been increased by vaccination, showed another increase because of the epidemc.