Although DNA plasmid and virus-like particle (VLP) vaccines have been individually tested against highly pathogenic avian influenza (HPAI) H5N1 viruses, the combination of both vaccines into a heterologous prime-boost strategy against HPAI H5N1 viruses has not been reported before. of homologous H5N1 challenge even when the challenge was administrated at 60 days post the boost.These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic

Buchy, Philippe

Deubel, Vincent

Ding, Heng

Gutiérrez, Ramona Alikiiteaga

Tsai, Cheguo

Zhou, Fan

Zhou, Paul

PLoS ONE

English

PubMed

Ding Heng

Tsai Cheguo

Gutiérrez Ramona Alikiiteaga

Zhou Fan

Buchy Philippe

Deubel Vincent

Zhou Paul

Public Library of Science (PLOS)

Superior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and Virus Like Particle Boost against HPAI H5N1 Virus

BACKGROUND: Although DNA plasmid and virus-like particle (VLP) vaccines have been individually tested against highly pathogenic avian influenza (HPAI) H5N1 viruses, the combination of both vaccines into a heterologous prime-boost strategy against HPAI H5N1 viruses has not been reported before. METHODOLOGY/PRINCIPAL FINDINGS: We constructed DNA plasmid encoding H5HA (A/Shenzhen/406H/06, subclade 2.3.4) and generated VLP expressing the same H5HA and N1NA. We then compared neutralizing antibody responses and immune protection elicited with heterologous DNA-VLP, homologous DNA-DNA and VLP-VLP prime-boost strategies against HPAI H5N1 viruses in mice. We demonstrate that DNA-VLP elicits the highest neutralizing antibody titers among the three prime-boost strategies, whereas DNA-DNA elicits higher neutralizing antibody titers than VLP-VLP. We show that although all three prime-boost strategies protect mice from death caused by 10 MLD(50) of homologous and heterologous H5N1 challenge, only DNA-VLP and DNA-DNA protect mice from infection as manifested by no weight loss and no lung pathology. In addition, we show that although DNA-VLP and DNA-DNA protect mice from death caused by 1,000 MLD(50) of homologous H5N1 challenge, only DNA-VLP protects mice from infection. Moreover, we show that after 1,000 MLD(50) of heterologous H5N1 challenge, while all mice in PBS, VLP-VLP and DNA-DNA died, 3 of 6 mice in DNA-VLP actually survived. Finally, we show that DNA-VLP completely protects mice from infection after 1,000 MLD(50) of homologous H5N1 challenge even when the challenge was administrated at 60 days post the boost. CONCLUSIONS/SIGNIFICANCE: These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic

Heng Ding

Cheguo Tsai

Ramona Alikiiteaga Gutiérrez

Fan Zhou

Philippe Buchy

Vincent Deubel

Paul Zhou

Directory of Open Access Journals

Superior neutralizing antibody response and protection in mice vaccinated with heterologous DNA prime and virus like particle boost against HPAI H5N1 virus.

International audienceBACKGROUND: Although DNA plasmid and virus-like particle (VLP) vaccines have been individually tested against highly pathogenic avian influenza (HPAI) H5N1 viruses, the combination of both vaccines into a heterologous prime-boost strategy against HPAI H5N1 viruses has not been reported before. METHODOLOGY/PRINCIPAL FINDINGS: We constructed DNA plasmid encoding H5HA (A/Shenzhen/406H/06, subclade 2.3.4) and generated VLP expressing the same H5HA and N1NA. We then compared neutralizing antibody responses and immune protection elicited with heterologous DNA-VLP, homologous DNA-DNA and VLP-VLP prime-boost strategies against HPAI H5N1 viruses in mice. We demonstrate that DNA-VLP elicits the highest neutralizing antibody titers among the three prime-boost strategies, whereas DNA-DNA elicits higher neutralizing antibody titers than VLP-VLP. We show that although all three prime-boost strategies protect mice from death caused by 10 MLD(50) of homologous and heterologous H5N1 challenge, only DNA-VLP and DNA-DNA protect mice from infection as manifested by no weight loss and no lung pathology. In addition, we show that although DNA-VLP and DNA-DNA protect mice from death caused by 1,000 MLD(50) of homologous H5N1 challenge, only DNA-VLP protects mice from infection. Moreover, we show that after 1,000 MLD(50) of heterologous H5N1 challenge, while all mice in PBS, VLP-VLP and DNA-DNA died, 3 of 6 mice in DNA-VLP actually survived. Finally, we show that DNA-VLP completely protects mice from infection after 1,000 MLD(50) of homologous H5N1 challenge even when the challenge was administrated at 60 days post the boost. CONCLUSIONS/SIGNIFICANCE: These results provide strong support for clinical evaluation of heterologous DNA-VLP prime-boost strategy as a public health intervention against a possible H5N1 pandemic

Hal-Diderot

Cumulative Number of Confirmed Human Cases of Avian Influenza

Establishment of multiple sublineages of H5N1 influenza virus in Asia: implications for pandemic control.

H5N1 outbreaks and enzootic influenza.

Organization Global Influenza Program Surveillance Network.

Writing Committee of the Second World Health Organization Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1) Virus.

Superior Neutralizing Antibody Response and Protection in Mice Vaccinated with Heterologous DNA Prime and Virus Like Particle Boost against HPAI H5N1 Virus

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Directory of Open Access Journals

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