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Influenza virus-like particle vaccines made in Nicotiana benthamiana elicit durable, poly-functional and cross-reactive T cell responses to influenza HA antigens

Clin Immunol. 2014 Oct;154(2):164-77. doi: 10.1016/j.clim.2014.08.003. Epub 2014 Aug 14.

Abstract

Cell-mediated immunity plays a major role in long-lived, cross-reactive protection against influenza virus. We measured long-term poly-functional and cross-reactive T cell responses to influenza hemagglutinin (HA) elicited by a new plant-made Virus-Like Particle (VLP) vaccine targeting either H1N1 A/California/7/09 (H1) or H5N1 A/Indonesia/5/05 (H5). In two independent clinical trials, we characterized the CD4(+) and CD8(+) T cell homotypic and heterotypic responses 6 months after different vaccination regimens. Responses of VLP-vaccinated subjects were compared with placebo and/or a commercial trivalent inactivated vaccine (TIV:Fluzone™) recipients. Both H1 and H5 VLP vaccines elicited significantly greater poly-functional CD4(+) T cell responses than placebo and TIV. Poly-functional CD8(+) T cell responses were also observed after H1 VLP vaccination. Our results show that plant-made HA VLP vaccines elicit both strong antibody responses and poly-functional, cross-reactive memory T cells that persist for at least 6 months after vaccination.

Keywords: Cell-mediated immunity; Influenza; Long-term memory response; Nicotiana benthamiana; Vaccine; Virus-like particle.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antigens, Viral / immunology*
  • Biomarkers
  • Female
  • Humans
  • Immunity, Cellular
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Male
  • Nicotiana / cytology*
  • Nicotiana / immunology
  • T-Lymphocytes / physiology*
  • Vaccines, Virus-Like Particle / immunology
  • Young Adult

Substances

  • Antigens, Viral
  • Biomarkers
  • Influenza Vaccines
  • Vaccines, Virus-Like Particle