Immunization with Cross-Conserved H1N1 Influenza CD4+ T-Cell Epitopes Lowers Viral Burden in HLA DR3 Transgenic Mice
Date of Original Version
Cell & Molecular Biology
The emergence of the pandemic H1N1 strain of influenza in 2009 was associated with a unique w-shaped age-related susceptibility curve, with higher incidence of morbidity and mortality among young persons and lower incidence among older persons, also observed during the 1918 influenza pandemic. Pre-existing H1N1 antibodies were not cross-reactive with the prior seasonal vaccine, forcing influenza experts to scramble to develop a new vaccine specific for the pandemic virus. We hypothesized that response to T-cell epitopes that are cross-conserved between pandemic H1N1 and the 2008 seasonal influenza vaccine strains might have contributed to partial protection from clinical illness among older adults, despite the lack of cross-reactive humoral immunity. Using immunoinformatics tools, we previously identified hemagglutinin and neuraminidase epitopes that were highly conserved between seasonal and pandemic H1N1. Here, we validated predicted CD4+ T-cell epitopes for their ability to bind HLA and to stimulate interferon-γ production in peripheral blood mononuclear cells from a cohort of donors presenting with influenza-like illness during the 2009 pandemic and a separate cohort immunized with trivalent influenza vaccine in 2011. A limited-epitope heterologous DNA-prime/peptide-boost vaccine composed of these sequences stimulated immune responses and lowered lung viral loads in HLA DR3 transgenic mice challenged with pandemic 2009 H1N1 influenza. Cross-priming with conserved influenza T-cell epitopes such as these may be critically important to T cell-mediated protection against pandemic H1N1 in the absence of cross-protective antibodies.
Moise, Leonard, Ryan Tassone, Howard Latimer, Frances Terry, Lauren Levitz, John P. Haran, Ted M. Ross, Christine Boyle, William D. Martin, and Anne S De Groot. "Immunization with Cross-Conserved H1N1 Influenza CD4+ T-Cell Epitopes Lowers Viral Burden in HLA DR3 Transgenic Mice." Human Vaccines & Immunotherapeutics 9.10 (2013): 2060-2068.
Available at: http://dx.doi.org/10.4161/hv.26511
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