Protective immunity against H5N1 influenza virus by a single dose vaccination with virus-like particles

• Authors: Jae-Min Song, Emory University; Md. Jaber Hossain, Centers for Disease Control and Prevention; Dae-Goon Yoo, Emory University; Aleksandr S. Lipatov, Centers for Disease Control and Prevention; C. Todd Davis, Centers for Disease Control and Prevention; Fu-Shi Quan, Emory University; Li-Mei Chen, Centers for Disease Control and Prevention; Jeff Hogan, University of Georgia at Athens; Ruben O. Donis, Emory University; Richard W Compans, Emory University; Sang-Moo Kang, Emory University
• Journal Title: Virology
• Volume: Volume 405, Number 1
• Publisher: Elsevier | 2010-09-15, Pages 165-175
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.virol.2010.05.034
• Subjects: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology
• Keywords: Virus like particles; subunit vaccine; influenza virus; H5N1; protection; memory immune responses

Abstract

We generated influenza virus-like particles (VLPs) containing the wild type (WT) H5 hemagglutinin (HA) from A/Viet Nam/1203/04 virus or a mutant H5 HA with a deletion of the multibasic cleavage motif. VLPs containing mutant H5 HA were found to be as immunogenic as VLPs containing WT HA. A single intramuscular vaccination with either type of H5 VLPs provided complete protection against lethal challenge. In contrast, the recombinant H5 HA vaccine was less immunogenic and vaccination even with 5 fold high dose did not induce protective immunity. VLP vaccines were superior to the recombinant HA in inducing T helper type 1 immune responses, hemagglutination inhibition titers, and antibody secreting cells, which significantly contribute to inducing protective immunity after a single dose vaccination. This study provides insights into the potential mechanisms of improved immunogenicity by H5 VLP vaccines as an approach to improve the protective efficacy against potential pandemic viruses.