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New progress on vaccine research against Highly Pathogenic Avian Influenza H5N1 Viruses

On April 10, Journal of Virology online published an article entitled “A Triclade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of Highly Pathogenic Avian Influenza H5N1 Viruses” by Professor Paul Zhou’s laboratory at the Institut Pasteur of Shanghai, Chinese Academy of Sciences. This is the first report that broadly neutralizing antibody responses against all clades and subclades of Highly Pathogenic Avian Influenza (HPAI) H5N1 viruses can be elicited with a vaccination.

Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds, and potential human-to-human transmission, HPAI H5N1 viruses remain a major global health concern. The high degree of genetic diversity also poses enormous challenge in developing effective vaccines. To overcome this, a Ph.D. student Fan Zhou and a research associate Quiqin Wang and others under the guidance of Professor Zhou took a new approach, i.e., the development of immunogens based on a comprehensive serologic study. Towards this goal, they constructed DNA plasmids encoding codon-optimized hemagglutinin (HA) from 17 representative strains covering all reported clades and subclades of HPAI H5N1 viruses. Using DNA plasmids, they generated the corresponding H5N1 pseudotypes and immune sera. They performed an across-the-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. They then designed a triclade DNA vaccine and evaluated its immunogenicity and protection in mice. They found that (sub)clades can be grouped into two major antigenic clusters and subclades and 7.2 were each by itself. Importantly, they demonstrated that the triclade DNA vaccine encoding HAs of (sub)clades 0,, and 7.2 elicited broadly neutralizing antibody responses against all H5 clades and subclades and protected mice against high-lethal-dose heterologous H5N1 challenge. Thus, they demonstrate that broadly neutralizing antibodies against all H5 clades and subclades can indeed be elicited with immunogens on the basis of a comprehensive serologic study. Further evaluation and optimization of such an approach in ferrets and in humans is warranted.

This research was in collaboration with Professor Vincent Deubel in Pasteur Institute in Cambodia and Professor Henry Wan in the State University in Missicipi, and supported by grants from the National Natural Science Foundation, National Science and Technology Major Projects and the ShanghaiPasteur Health Research Foundation.

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