Giuseppe
Emeritus
[Source: The Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
DNA Prime and Virus-like Particle Boost from a Single H5N1 Strain Elicits Broadly Neutralizing Antibody Responses against Head Region of H5 Hemagglutinin
Guiqin Wang 1, Fan Zhou 1, Philippe Buchy 2, Teng Zuo 3, Hongxing Hu 1, Jingjing Liu 1, Yufeng Song 1, Heng Ding 1, Cheguo Tsai 1, Ze Chen 4, Linqi Zhang 3, Vincent Deubel 2 and Paul Zhou 1,#
Author Affiliations: <SUP>1</SUP>The Unit of Anti-viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025 <SUP>2</SUP>Institut Pasteur in Cambodia, Phnom Penh, Cambodia <SUP>3</SUP>Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing, China 100084 <SUP>4</SUP>Shanghai Institute of Biological Products, Shanghai, China
#Corresponding author: Paul Zhou, the Unit of Anti-viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025, blzhou@sibs.ac.cn, Fax: 8621-63843571, Tel.86163851390.
Abstract
Since 1996 highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with VLP induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and post-attachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.
Received April 2, 2013. Revision received June 25, 2013. Accepted July 1, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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DNA Prime and Virus-like Particle Boost from a Single H5N1 Strain Elicits Broadly Neutralizing Antibody Responses against Head Region of H5 Hemagglutinin
Guiqin Wang 1, Fan Zhou 1, Philippe Buchy 2, Teng Zuo 3, Hongxing Hu 1, Jingjing Liu 1, Yufeng Song 1, Heng Ding 1, Cheguo Tsai 1, Ze Chen 4, Linqi Zhang 3, Vincent Deubel 2 and Paul Zhou 1,#
Author Affiliations: <SUP>1</SUP>The Unit of Anti-viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025 <SUP>2</SUP>Institut Pasteur in Cambodia, Phnom Penh, Cambodia <SUP>3</SUP>Comprehensive AIDS Research Center, School of Medicine, Tsinghua University, Beijing, China 100084 <SUP>4</SUP>Shanghai Institute of Biological Products, Shanghai, China
#Corresponding author: Paul Zhou, the Unit of Anti-viral Immunity and Genetic Therapy, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China 200025, blzhou@sibs.ac.cn, Fax: 8621-63843571, Tel.86163851390.
Abstract
Since 1996 highly pathogenic avian influenza (HPAI) H5N1 virus has presented a persistent threat to public health. Its high degree of genetic diversity also poses enormous challenges in developing effective vaccines. To search for vaccine regimens that could elicit broadly neutralizing antibody responses against diverse HPAI H5N1 strains, in the present study we tested H5 hemagglutinin (HA) from an A/Thailand/1(KAN)-1/2004 strain in a heterologous prime-boost vaccination. We demonstrated that priming mice with DNA and boosting with VLP induced antibody responses that cross-neutralize all reported clades and subclades of HPAI H5N1 viruses and protect mice from high lethal dose HPAI H5N1 challenge in both active and passive immunizations. Unexpectedly, cross-divergent H5 neutralizing antibodies are directed to the HA head and block both attachment and post-attachment of virus entry. Thus, we conclude that as a promising pan-H5 vaccine candidate this prime-boost regimen could be further developed in ferrets and in humans.
Received April 2, 2013. Revision received June 25, 2013. Accepted July 1, 2013.
? The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
For Permissions, please e-mail: journals.permissions@oup.com.
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