RGD capsid modification enhances mucosal protective immunity of a non-human primate adenovirus vector expressing Pseudomonas aeruginosa OprF. Academic Article Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Cells, Cultured
  • Cytokines
  • Female
  • Genetic Vectors
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin G
  • Mice
  • Mice, Inbred C57BL
  • Primates
  • Pseudomonas Vaccines

MeSH Major

  • CD8-Positive T-Lymphocytes
  • Lung
  • Oligopeptides
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • Th1 Cells

abstract

  • Replication-deficient adenoviral (Ad) vectors of non-human serotypes can serve as Ad vaccine platforms to circumvent pre-existing anti-human Ad immunity. We found previously that, in addition to that feature, a non-human primate-based AdC7 vector expressing outer membrane protein F of P. aeruginosa (AdC7OprF) was more potent in inducing lung mucosal and protective immunity compared to a human Ad5-based vector. In this study we analysed if genetic modification of the AdC7 fibre to display an integrin-binding arginine-glycine-aspartic acid (RGD) sequence can further enhance lung mucosal immunogenicity of AdC7OprF. Intratracheal immunization of mice with either AdC7OprF.RGD or AdC7OprF induced robust serum levels of anti-OprF immunoglobulin (Ig)G up to 12 weeks that were higher compared to immunization with the human vectors Ad5OprF or Ad5OprF.RGD. OprF-specific cellular responses in lung T cells isolated from mice immunized with AdC7OprF.RGD and AdC7OprF were similar for T helper type 1 (Th1) [interferon (IFN)-γ in CD8(+) and interleukin (IL)-12 in CD4(+)], Th2 (IL-4, IL-5 and IL-13 in CD4(+)) and Th17 (IL-17 in CD4(+)). Interestingly, AdC7OprF.RGD induced more robust protective immunity against pulmonary infection with P. aeruginosa compared to AdC7OprF or the control Ad5 vectors. The enhanced protective immunity induced by AdC7OprF.RGD was maintained in the absence of alveolar macrophages (AM) or CD1d natural killer T cells. Together, the data suggest that addition of RGD to the fibre of an AdC7-based vaccine is useful to enhance its mucosal protective immunogenicity. © 2013 British Society for Immunology.

publication date

  • August 2013

has subject area

  • Adenoviridae
  • Animals
  • CD8-Positive T-Lymphocytes
  • Cells, Cultured
  • Cytokines
  • Female
  • Genetic Vectors
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin G
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Oligopeptides
  • Porins
  • Primates
  • Pseudomonas Infections
  • Pseudomonas Vaccines
  • Pseudomonas aeruginosa
  • Th1 Cells

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3722923

Digital Object Identifier (DOI)

  • 10.1111/cei.12101

PubMed ID

  • 23607394

Additional Document Info

start page

  • 230

end page

  • 241

volume

  • 173

number

  • 2