Antibody responses and protection against influenza virus infection in different congenic strains of mice immunized intranasally with adjuvant-combined A/Beijing/262/95 (H1N1) virus hemagglutinin or neuraminidase

Abstract

Antibody (Ab) responses and protection against influenza virus infection in mice immunized intranasally with hemagglutinin (HA) or neuraminidase (NA) purified from the A/Beijing/262/95 (A/Beijing) (H1N1) virus were compared among B10 congenic mouse strains. Mice were immunized intranasally with 0.1, 0.3 or 1microg of HA or NA together with the cholera toxin adjuvant, and then boosted intranasally with 0.3 microg of the adjuvant-combined HA or NA 4 weeks later. Two weeks after the second immunization, the mice were challenged by an infection of the upper respiratory tract with the homologous virus. After 3 days, nasal wash and serum specimens were collected for virus and Ab titration. The HA immunization induced HA-specific IgG Ab responses against A/Beijing HA, which depended on the H-2 haplotype of the strain: The B10.A (H-2(a)), B10.D2 (H-2(d)), B10.BR (H-2(k)) and B10 (H-2(b)) strains were the highest, high, intermediate and low responders, respectively. The nasal IgA responses were induced in the B10.A, B10.D2 and B10.BR strains, but not in the B10 strain. In parallel with Ab responses, the B10.A, B10.BR and B10.D2 strains were conferred significant protection at any dose of primary immunization, but the B10 strain was provided protection only at 1microg of HA. On the other hand, the NA immunization induced NA-specific Ab responses, which depended on the the H-2 haplotype of the strain: the B10.A, B10.D2, B10 and B10.BR strains were the highest, high, intermediate and low responders, respectively. In parallel with Ab responses, all the strains were conferred significant protection at any dose of primary immunization. These results indicate that the MHC-restricted responsiveness of mice to HA is different from that to NA, suggesting that the use of high-HA dose or NA as a component of the nasal influenza A (H1N1 subtype) virus vaccine improves the protective efficacy against influenza among low responder populations.