Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF. Academic Article Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Female
  • Genetic Vectors
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin A
  • Immunoglobulin G
  • Interferon-gamma
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes

MeSH Major

  • Immunity, Mucosal
  • Lung
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa

abstract

  • Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p>0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p>0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (p<0.05). Interestingly, direct administration of AdC7OprF to the respiratory tract resulted in an increase of OprF-specific IgG in serum, OprF-specific IgG and IgA in lung ELF, and OprF-specific INF-γ in lung T-cells compared to immunization with Ad5OprF, and survival following challenge with a lethal dose of P. aeruginosa. These data demonstrate that systemic or lung mucosal immunization with an AdC7-based vaccine vector induces superior pulmonary humoral and cellular anti-transgene immunity compared to immunization with an Ad5-based vector and favors AdC7-based vectors as vaccines to induce lung mucosal immunity. Copyright © 2010 Elsevier Ltd. All rights reserved.

publication date

  • March 3, 2011

has subject area

  • Adenoviridae
  • Animals
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Female
  • Genetic Vectors
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunity, Mucosal
  • Immunoglobulin A
  • Immunoglobulin G
  • Interferon-gamma
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • T-Lymphocytes

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3061442

Digital Object Identifier (DOI)

  • 10.1016/j.vaccine.2010.12.087

PubMed ID

  • 21215829

Additional Document Info

start page

  • 2131

end page

  • 2139

volume

  • 29

number

  • 11