Induction of Long-Term Protective Immune Responses by Influenza H5N1 Virus-Like Particles |
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| Authors: | Sang-Moo Kang Dae-Goon Yoo Aleksandr S Lipatov Jae-Min Song C Todd Davis Fu-Shi Quan Li-Mei Chen Ruben O Donis Richard W Compans |
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| Institution: | 1. Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America.; 2. Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.;Karolinska Institutet, Institution for Laboratory Medicine, Sweden |
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| Abstract: | BackgroundRecurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Methodology/Principal FindingsInfluenza virus-like particles (VLPs) produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1) hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.Conclusions/SignificanceThese results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza. |
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