tetano
Editor, Senior Moderator
J Virol. 2012 Apr 11. [Epub ahead of print]
A Tri-Clade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of HPAI H5N1 Viruses.
Zhou F, Wang G, Buchy P, Cai Z, Chen H, Chen Z, Cheng G, Wan XF, Deubel V, Zhou P.
Source
Unit of anti-viral Immunity and Genetic therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, South Chongqing Road, Shanghai, China 200025.
Abstract
Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. High degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, in this study we took a new approach, i.e. development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized HA from 17 representative strains covering all reported clades and subclades of HPAI H5N1 viruses. Using DNA plasmids we generated corresponding H5N1 pseudotypes and immune sera. We performed an across-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a tri-clade DNA vaccine and evaluated its immunogenicity and protection in mice. Here we report that (sub)clades 0, 1, 3, 4, 5, 6, 7.1 and 9 were grouped into antigenic cluster 1; (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5 and 8 into another with subclade 2.2.1 loosely connected to it; and subclades 2.3.2.1 and 7.2 each by itself. Importantly, the tri-clade DNA vaccine encoding HA of (sub)clades 0, 2.3.2.1 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, we conclude 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.
PMID:
22496212
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22496212
A Tri-Clade DNA Vaccine Designed on the Basis of a Comprehensive Serologic Study Elicits Neutralizing Antibody Responses against All Clades and Subclades of HPAI H5N1 Viruses.
Zhou F, Wang G, Buchy P, Cai Z, Chen H, Chen Z, Cheng G, Wan XF, Deubel V, Zhou P.
Source
Unit of anti-viral Immunity and Genetic therapy, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, South Chongqing Road, Shanghai, China 200025.
Abstract
Because of their rapid evolution, genetic diversity, broad host range, ongoing circulation in birds and potential human-to-human transmission, H5N1 influenza viruses remain a major global health concern. High degree of genetic diversity also poses enormous burdens and uncertainties in developing effective vaccines. To overcome this, in this study we took a new approach, i.e. development of immunogens based on a comprehensive serologic study. We constructed DNA plasmids encoding codon-optimized HA from 17 representative strains covering all reported clades and subclades of HPAI H5N1 viruses. Using DNA plasmids we generated corresponding H5N1 pseudotypes and immune sera. We performed an across-board pseudotype-based neutralization assay and determined antigenic clusters by cartography. We then designed a tri-clade DNA vaccine and evaluated its immunogenicity and protection in mice. Here we report that (sub)clades 0, 1, 3, 4, 5, 6, 7.1 and 9 were grouped into antigenic cluster 1; (sub)clades 2.1.3.2, 2.3.4, 2.4, 2.5 and 8 into another with subclade 2.2.1 loosely connected to it; and subclades 2.3.2.1 and 7.2 each by itself. Importantly, the tri-clade DNA vaccine encoding HA of (sub)clades 0, 2.3.2.1 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, we conclude 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.
PMID:
22496212
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22496212