Abstract
Background: The direct transmission of avian influenza H5N1 virus from infected poultry into humans raised questions about the level of protection induced by different strains within the H5 subtype. Methods: In this study, the hemagglutinins (HA) of four avian H5 viruses and the human A/Hong Kong/156/97 (H5N1) strain were analyzed antigenically and their phylogenetic relationships were established. These viruses were further characterized in cross-protection studies in mice. Mice were immunized with β-propiolactone-inactivated viruses, and three weeks later challenged with 10 MLD 50 of the mouse-adapted A/Mallard Duck/Pennsylvania/10218/84. Results: The HI test with a panel of HA-specific monoclonal antibodies showed different reactivity patterns for the five H5 influenza viruses studied. Phylogenetic analysis revealed genetic diversity among these H5 viruses as well. Cross-protection experiments indicated that mice immunized with American viruses exhibited a high level of protection (94.4–100.0%) against challenge with the virus from the same phylogenetic lineage. Immunization with Eurasian viruses induced lower levels of protection in mice (50.0–55.5%). Conclusions: Due to the heterogeneity of the H5 viruses, no single broad reactive strain is available as an appropriate vaccine candidate for a potential H5 influenza pandemic.
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