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Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination
Penghui Yang1#, Yueqiang Duan1#, Peirui Zhang2#, Zhiwei Li2, Cheng Wang3, Mei Dong1, Chong Tang1, Li Xing1, Hongjing Gu1, Zhongpeng Zhao1, Xiufan Liu4, Shaogeng Zhang2*, Xiliang Wang1*
1 Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China, 2 Department of Hepatobiliary, 302 Military Hospital, Beijing, China, 3 Medical College of Soochow University, Suzhou, China, 4 Key Laboratory for Animal Infectious Diseases of Ministry of Agriculture, Yangzhou University, Yangzhou, China
Abstract Top
Background
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.
Methodology/Principal Findings
Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 ?g 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 ?g 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/Significance
Our 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.
Citation: Yang P, Duan Y, Zhang P, Li Z, Wang C, et al. (2012) Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination. PLoS ONE 7(1): e30252. doi:10.1371/journal.pone.0030252
Editor: Yi Guan, The University of Hong Kong, China
Received: August 1, 2011; Accepted: December 15, 2011; Published: January 18, 2012
Penghui Yang1#, Yueqiang Duan1#, Peirui Zhang2#, Zhiwei Li2, Cheng Wang3, Mei Dong1, Chong Tang1, Li Xing1, Hongjing Gu1, Zhongpeng Zhao1, Xiufan Liu4, Shaogeng Zhang2*, Xiliang Wang1*
1 Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China, 2 Department of Hepatobiliary, 302 Military Hospital, Beijing, China, 3 Medical College of Soochow University, Suzhou, China, 4 Key Laboratory for Animal Infectious Diseases of Ministry of Agriculture, Yangzhou University, Yangzhou, China
Abstract Top
Background
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.
Methodology/Principal Findings
Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 ?g 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 ?g 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/Significance
Our 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.
Citation: Yang P, Duan Y, Zhang P, Li Z, Wang C, et al. (2012) Multiple-Clade H5N1 Influenza Split Vaccine Elicits Broad Cross Protection against Lethal Influenza Virus Challenge in Mice by Intranasal Vaccination. PLoS ONE 7(1): e30252. doi:10.1371/journal.pone.0030252
Editor: Yi Guan, The University of Hong Kong, China
Received: August 1, 2011; Accepted: December 15, 2011; Published: January 18, 2012