title: Cross-conservation of T-cell epitopes: now even more relevant to (H7N9) influenza vaccine design.
abstract: A novel avian-origin H7N9 influenza strain emerged in China in April 2013. Since its re-emergence in October-November 2013, the number of reported cases has accelerated; more than 220 laboratory-confirmed cases and 112 deaths (case fatality rate of 20-30%) have been reported. The resurgence of H7N9 has re-emphasized the importance of making faster and more effective influenza vaccines than those that are currently available. Recombinant H7 hemagglutinin (H7-HA) vaccines have been produced, addressing the first problem. Unfortunately, these recombinant subunit vaccine products appear to have failed to address the second problem, influenza vaccine efficacy. Reported unadjuvanted H7N9 vaccine seroconversion rates were between 6% and 16%, nearly 10-fold lower than rates for unadjuvanted vaccine seroconversion to standard H1N1 monovalent (recombinant) vaccine (89% to pandemic H1N1). Could this state of affairs have been predicted? As it turns out, yes, and it was. In that previous analysis of available H7-HA sequences, we found fewer T-cell epitopes per protein than expected, and predicted that H7-HA-based vaccines would be much less antigenic than recent seasonal vaccines. Novel approaches to developing a more immunogenic HA were offered for consideration at the time, and now, as the low immunogenicity of H7N9 vaccines appears to indicate, they appear to be even more relevant. More effective H7N9 influenza vaccines can be produced, provided that the role of T-cell epitopes is carefully considered, and accumulated knowledge about the importance of cross-conserved epitopes between viral subtypes is applied to the design of those vaccines.
authors: Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA; EpiVax, Inc.; Providence, RI USA.
authors: Anne S
authors: AS
authors: De Groot
authors: Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA; EpiVax, Inc.; Providence, RI USA.
authors: Lenny
authors: L
authors: Moise
authors: Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA.
authors: Rui
authors: R
authors: Liu
authors: Institute for Immunology and Informatics; University of Rhode Island; Providence, RI USA.
authors: Andres H
authors: AH
authors: Gutierrez
authors: EpiVax, Inc.; Providence, RI USA.
authors: Frances
authors: F
authors: Terry
authors: Laboratory of Applied Molecular Biology; University of Bamako; Bamako, Mali; Project SEREFO-NIAID (Centre de Recherche et de Formation sur le VIH/Sida et la Tuberculose-Institut National des Maladies Infectieuses et Allergiques); University of Science, Techniques and Technologies of Bamako; Bamako, Mali.
authors: Ousmane A
authors: OA
authors: Koita
authors: Vaccine and Gene Therapy Institute of Florida; Port St. Lucie, FL USA.
authors: Ted M
authors: TM
authors: Ross
authors: EpiVax, Inc.; Providence, RI USA.
authors: William
authors: W
authors: Martin
mesh_terms: D000818:Animals; D002681:China / Q000453:epidemiology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D007251:Influenza, Human / Q000453:epidemiology* / Q000517:prevention & control* / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C109963:hemagglutinin, avian influenza A virus
keywords: CD4+ T cell; H1N1; H7N9; T cell; T helper; T-cell epitope; avian-origin; cell-mediated immunity; genome; hemagglutinin; influenza; recombinant protein