期刊
ANTIVIRAL RESEARCH
卷 148, 期 -, 页码 43-52出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2017.10.018
关键词
Recombinant influenza virus; Viral vector; Chimeric M2e4x-HA protein; Universal influenza vaccine
资金
- NIH/NIAID [AI119366, AI105170, AI093772]
- Animal and Plant Quarantine Agency, Republic of Korea [I-1541781-2012-15-01]
- NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: A/PR8 HA specific monoclonal antibody [IC5-4F8]
Current influenza vaccines provide hemagglutinin (HA) strain-specific protection. To improve cross protection, we engineered replication-competent influenza A virus to express tandem repeats of heterologous M2 extra cellular (M2e) domains in a chimeric HA. M2e epitopes conjugated to HA glycoproteins (M2e4x-HA) were found to be expressed on the surfaces of a replicable influenza virus as examined by electron microscopy. The recombinant influenza virus containing M2e4x-HA was moderately attenuated but superior to the parental virus in inducing M2e specific antibodies without compromising HA immunogenicity. Recombinant influenza virus immune mice showed better cross protection than parental virus immune mice. Immune sera from the mice with inoculation of live recombinant influenza virus expressing M2e4x-HA were effective in conferring protection against H1, H3, and H5 subtype influenza viruses. This study indicates that recombinant influenza virus expressing conserved protective epitopes in an HA chimeric form can provide a new approach for improving the efficacy of influenza vaccines.
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