Adenovirus-based vaccine with epitopes incorporated in novel fiber sites to induce protective immunity against Pseudomonas aeruginosa. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigen Presentation
  • Female
  • Genetic Vectors
  • Immunity, Cellular
  • Immunity, Humoral
  • Lung
  • Mice
  • Models, Molecular
  • Protein Structure, Secondary
  • Respiratory Mucosa

MeSH Major

  • Adenoviridae
  • Capsid Proteins
  • Epitopes
  • Pseudomonas Infections
  • Pseudomonas Vaccines
  • Pseudomonas aeruginosa

abstract

  • Adenovirus (Ad) vector-based vaccines displaying pathogen-derived epitopes on Ad capsid proteins can elicit anti-pathogen immunity. This approach seems to be particularly efficient with epitopes incorporated into the Ad fiber protein. Here, we explore epitope insertion into various sites of the Ad fiber to elicit epitope-specific immunity. Ad vectors expressing the 14-mer Pseudomonas aeruginosa immune-dominant outer membrane protein F (OprF) epitope 8 (Epi8) in five distinct sites of the Ad5 fiber, loops CD (AdZ.F(CD)Epi8), DE (AdZ.F(DE)Epi8), FG (AdZ.F(FG)Epi8), HI (AdZ.F(HI)Epi8) and C terminus (AdZ.F(CT)Epi8), or the hexon HVR5 loop (AdZ.HxEpi8) were compared in their capacity to elicit anti-P. aeruginosa immunity to AdOprF, an Ad expressing the entire OprF protein. Intramuscular immunization of BALB/c mice with AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8 elicited higher anti-OprF humoral and cellular CD4 and CD8 responses as well as enhanced protection against respiratory infection with P. aeruginosa compared to immunization with AdZ.F(CD)Epi8, AdZ.F(DE)Epi8, AdZ.F(CT)Epi8 or AdZ.HxEpi8. Importantly, repeat administration of the fiber- and hexon-modified Ad vectors boosted the OprF-specific humoral immune response in contrast to immunization with AdOprF. Strikingly, following three doses of AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8 anti-OprF immunity surpassed that induced by AdOprF. Furthermore, in the presence of anti-Ad5 immunity, immunization with AdZ.F(FG)Epi8 or AdZ.F(HI)Epi8, but not with AdOprF, induced protective immunity against P. aeruginosa. This suggests that incorporation of epitopes into distinct sites of the Ad fiber is a promising vaccine strategy.

publication date

  • 2013

has subject area

  • Adenoviridae
  • Animals
  • Antigen Presentation
  • Capsid Proteins
  • Epitopes
  • Female
  • Genetic Vectors
  • Immunity, Cellular
  • Immunity, Humoral
  • Lung
  • Mice
  • Models, Molecular
  • Protein Structure, Secondary
  • Pseudomonas Infections
  • Pseudomonas Vaccines
  • Pseudomonas aeruginosa
  • Respiratory Mucosa

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3577763

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0056996

PubMed ID

  • 23437292

Additional Document Info

start page

  • e56996

volume

  • 8

number

  • 2