Differences in antibody responses of mice to intranasal or intraperitoneal immunization with influenza A virus and vaccination with subunit influenza vaccine

Two antigenically related but different influenza A virus strains of H3N2 subtype, A/Dunedin/ 4/73 (H3N2) (Dunedin) and A/Mississippi/1/85 (H3N2) (Mississippi), were used for intranasal (i.n.) and intraperitoneal (i.p.) immunization of mice and respective antibody responses were compared. In ELISA, using purified influenza A virus as antigen, the highest titer of antiviral antibodies was observed after a repeated i.n. infection, in which the Dunedin strain was followed by the Mississippi strain and vice versa. Similarly, in virus neutralization (VN) test, the highest titer of VN antibodies was found after a repeated i.n. infection. The subunit vaccine INFLUVAC, when administered intramuscularly (i.m.), induced only a poor antibody response as assayed by ELISA. Moreover, the INFLUVAC vaccination elicited a 100-fold lower titer of VN antibodies than the i.n. infection and an approx a 10-fold lower titer than the i.p. immunization. A repeated INFLUVAC vaccination did not lead to a significant increase of VN antibody titer. Also the antibody response to HA2gp--a conserved part of influenza hemagglutinin (HA) that might contribute to the induction of specific antiviral antibodies--was followed. Similarly to the VN antibody response, the highest HA2 antibody titer was induced after a repeated i.n. infection, whereas the lowest HA2 antibody titer was observed after a single or repeated INFLUVAC vaccination. Overall, the HA2 antibody titers remarkably well corresponded to the VN potential of the examined sera.