Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.
Merika T KodayJolie A LeonardPaul MunsonAdriana ForeroMichael KodayDebra L BrattJames T FullerRobert MurnaneShulin QinTodd A ReinhartKaren DuusIlhem MessaoudiAmy L HartmanKelly Stefano-ColeJuliet MorrisonMichael G KatzeDeborah Heydenburg FullerPublished in: PloS one (2017)
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.
Keyphrases
- circulating tumor
- sars cov
- cell free
- single molecule
- diabetic rats
- high glucose
- oxidative stress
- magnetic resonance
- coronavirus disease
- drug induced
- escherichia coli
- magnetic resonance imaging
- dengue virus
- computed tomography
- zika virus
- atomic force microscopy
- dendritic cells
- saccharomyces cerevisiae
- sensitive detection
- loop mediated isothermal amplification