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PLoS One. 2017 Dec 21;12(12):e0189780. doi: 10.1371/journal.pone.0189780. eCollection 2017.

Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.

Author information

1
Department of Microbiology, University of Washington, Seattle, WA, United States of America.
2
Washington National Primate Research Center, University of Washington, Seattle, WA, United States of America.
3
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States of America.
4
Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY, United States of America.
5
Basic Sciences Department, College of Osteopathic Medicine, Touro University Nevada, Henderson, NV, United States of America.
6
Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, OR, United States of America.

Abstract

Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA) universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

PMID:
29267331
PMCID:
PMC5739435
DOI:
10.1371/journal.pone.0189780
[Indexed for MEDLINE]
Free PMC Article

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