Immunogenicity of low-pH treated whole viral influenza vaccine

• Type of Material: Article
• Authors: Fu-Shi Quan, Emory University; Zhu-Nan Li, Emory University; Min-Chul Kim, Emory University; Dan Yang, Emory University; Richard W Compans, Emory University; David Steinhauer, Emory University; Sang-Moo Kang, Emory University
• Language: English
• Date: 2011-08-15
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2011.05.014
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 417
• Issue: 1
• Start Page: 196
• End Page: 202
• Grant/Funding Information: This work was supported in part by NIH/NIAID grant AI0680003 (R.W.C.), NIH/NIAID contract HHSN2662007000006C (D.A.S.), the Georgia Research Alliance (S.M.K), and NIH/NIAID grants AI081385 (S.M.K.) and AI093772 (S.M.K.).
• Keywords: Low pH; influenza; conformational change; vaccine; immunogenicity
• Research Categories: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology

Abstract

Low pH treatment of influenza virus hemagglutinin (HA) exposes its relatively conserved stalk domain, suggesting a potential immunogen with capability to induce broader immune responses. Here, we describe characterization, immunogenicity, antigenicity, and protective immunity induced by low pH treated inactivated whole viral vaccine in comparison with the untreated vaccine. The acidic pH treated viral vaccine showed high susceptibility to proteolytic cleavage and low hemagglutination activity indicating conformational changes. Immunization of mice with low pH treated viral vaccine induced lower levels of homologous or heterologous virus-specific binding and neutralizing antibodies compared to the untreated vaccine. Also, low pH treated influenza viral antigen showed lower antigenicity compared to the untreated influenza viral antigen. Lower efficacy of cross-protection against heterosubtypic virus was observed in the low-pH treated vaccine group. The results provide evidence that there is a correlation between protective efficacy and the stability of vaccines.