Protective immunity to pseudomonas aeruginosa induced with a capsid-modified adenovirus expressing P. aeruginosa OprF. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antibodies, Bacterial
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Capsid
  • Cell Line
  • Female
  • Genetic Vectors
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Pseudomonas Infections

MeSH Major

  • Adenoviridae
  • Bacterial Proteins
  • Capsid Proteins
  • Porins
  • Pseudomonas aeruginosa

abstract

  • This study focuses on the development of a new clinical vaccine candidate (AdOprF.RGD.Epi8) against Pseudomonas aeruginosa using an E1(-) E3(-) adenovirus (Ad) vector expressing OprF (AdOprF.RGD.Epi8) and modifications of the Ad genome providing two capsid changes: (i) modification of the Ad hexon gene to incorporate an immune-dominant OprF epitope (Epi8) into loop 1 of the hexon, enabling repeat administration to boost the anti-OprF immune response, and (ii) modification of the fiber gene to incorporate an integrin-binding RGD sequence to enhance gene delivery to antigen-presenting cells. Western analysis confirmed that AdOprF.RGD.Epi8 expresses OprF, contains Epi8 in the hexon protein, and enhances gene transfer to dendritic cells compared to AdOprF, a comparable Ad vector expressing OprF with an unmodified capsid. Intramuscular immunization of C57BL/6 mice with AdOprF.RGD.Epi8 resulted in the generation of anti-OprF antibodies at comparable levels to those induced following immunization with AdOprF, but immunization with AdOprF.RGD.Epi8 was associated with increased CD4 and CD8 gamma interferon T-cell responses against OprF as well as increased survival against lethal pulmonary challenge with agar-encapsulated P. aeruginosa. Importantly, repeat administration of AdOprF.RGD.Epi8 resulted in boosting of the humoral anti-OprF response as well as increased protection, whereas no boosting could be achieved with repeat administration of AdOprF. This suggests that the capsid-modified AdOprF.RGD.Epi8 vector is a more effective immunogen compared to a comparable wild-type Ad capsid, making it a good candidate for an anti-P. aeruginosa vaccine.

publication date

  • December 2007

has subject area

  • Adenoviridae
  • Animals
  • Antibodies, Bacterial
  • Bacterial Proteins
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Capsid
  • Capsid Proteins
  • Cell Line
  • Female
  • Genetic Vectors
  • Immunization
  • Mice
  • Mice, Inbred C57BL
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2168865

Digital Object Identifier (DOI)

  • 10.1128/JVI.01246-07

PubMed ID

  • 17942539

Additional Document Info

start page

  • 13801

end page

  • 13808

volume

  • 81

number

  • 24