Antibodies and CD4+ T-cells mediate cross-protection against H5N1 influenza virus infection in mice after vaccination with a low pathogenic H5N2 strain

A H5N2 low pathogenic avian influenza virus (LPAIV) was isolated from a natural reservoir in Bavaria during a routine screen and was used as a vaccine strain to scrutinize the immune response involved in cross-protection after challenge infection with a H5N1 highly pathogenic avian influenza virus (HPAIV). The challenge virus was also isolated from a natural reservoir in Bavaria. Wild type, antibody deficient (μMT), CD4−/− and CD8−/− mice were infected with the apathogenic H5N2 vaccine strain and challenge infection with a 100-fold MLD50 of the H5N1 strain was performed 80 days later. While 100% of the wild type and 100% of the CD8−/− mice stayed healthy, only 50% of the CD4−/− and none of the antibody deficient mice were protected. These results support the view that the humoral immune response and to certain extends the CD4+ T helper cells are a prerequisite for cross-protective immunity against H5 influenza virus.