An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus.

Guangyu Zhao 1 Shihui Sun 1 Lanying Du 2 Wenjun Xiao 1 Zhitao Ru 1 Zhihua Kou 1 Yan Guo 1 Hong Yu 1 Shibo Jiang 2 Yuchun Lone 3 Bo-Jian Zheng 4 Yusen Zhou 1, *
* Auteur correspondant
1 State Key Laboratory of Pathogen and Biosecurity
2 Lindsley F. Kimball Research Institute
3 Régulation de la survie cellulaire et des allogreffes
4 Department of Microbiology
Abstract : BACKGROUND: A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI) H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP) vaccine based on the extracellular domain of M2 protein (M2e) from H5N1 virus (H5N1-M2e-MAP) induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus. RESULTS: Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus. CONCLUSIONS: Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.
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Virology Journal, BioMed Central, 2010, 7 (1), pp.151. 〈10.1186/1743-422X-7-151〉
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Guangyu Zhao, Shihui Sun, Lanying Du, Wenjun Xiao, Zhitao Ru, et al.. An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus.. Virology Journal, BioMed Central, 2010, 7 (1), pp.151. 〈10.1186/1743-422X-7-151〉. 〈inserm-00668214〉

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