Multiple-clade H5N1 influenza split vaccine elicits broad cross protection against lethal influenza virus challenge in mice by intranasal vaccination.

Penghui Yang,Xiufan Liu,Hongjing Gu,Zhongpeng Zhao,Yueqiang Duan,Zhiwei Li,Mei Dong,Chong Tang,Li Xing,Cheng Wang,Peirui Zhang,Xiliang Wang,Shaogeng Zhang,Yi Guan

doi:10.1371/journal.pone.0030252

Penghui Yang, Xiufan Liu + Show 12 more

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https://doi.org/10.1371/journal.pone.0030252

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Abstract

BackgroundThe increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model.Methodology/Principal FindingsMice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 µg HA per dose) included rg-A/Vietnam/1203/2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 µg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60% in single A/Anhui/1/2005 vaccine group.Conclusion/SignificanceOur findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination against unknown pandemic virus.

Highlights

Influenza infection continues to be a major threat to human health on several fronts
Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous highly pathogenic avian influenza (HPAI) H5N1 virus, giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak
Sera collected at pretest and 14 days after the first and second doses of vaccine were assayed for the presence of H5N1 influenzaspecific antibodies using a hemagglutination inhibition (HI) assay

Summary

Introduction

Influenza infection continues to be a major threat to human health on several fronts. As of 29 Nov. 2011, the World Health Organization (WHO) has reported 571 laboratory-confirmed cases of human A/ H5N1 infections, resulting in 335 deaths (http://www.who.int/csr/ disease/avian_influenza/country/cases_table_2011_01_20/en/index.html). A great concern exists that the reassortants between avian H5N1 and influenza A (H1N1), seasonal viruses or changing receptor binding specificity of H5 might be of great impact to human health, once it acquires the capability of human-to-human transmission [4]. The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model

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Conclusion