Replacing adenoviral vector HVR1 with a malaria B cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antibodies, Protozoan
  • Base Sequence
  • Cell Line, Tumor
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data

MeSH Major

  • Adenoviridae
  • Capsid Proteins
  • Epitopes, B-Lymphocyte
  • Genetic Vectors
  • Plasmodium yoelii
  • Protozoan Proteins

abstract

  • Although adenovirus (Ad) has been regarded as an excellent vaccine vector, there are 2 major drawbacks to using this platform: (a) Ad-based vaccines induce a relatively weak humoral response against encoded transgenes, and (b) preexisting immunity to Ad is highly prevalent among the general population. To overcome these obstacles, we constructed an Ad-based malaria vaccine by inserting a B cell epitope derived from a Plasmodium yoelii circumsporozoite (CS) protein (referred to as the PyCS-B epitope) into the capsid proteins of WT/CS-GFP, a recombinant Ad expressing P. yoelii CS protein and GFP as its transgene. Multiple vaccinations with the capsid-modified Ad induced a substantially increased level of protection against subsequent malaria challenge in mice when compared with that of unmodified WT/CS-GFP. Increased protection correlated with augmented antibody responses against the PyCS-B epitope expressed in the capsid. Furthermore, replacement of hypervariable region 1 (HVR1) of the Ad capsid proteins with the PyCS-B epitope circumvented neutralization of the modified Ad by preexisting Ad-specific antibody, both in vivo and in vitro. Importantly, the immunogenicity of the Ad-containing PyCS-B epitope in the HVR1 and a P. yoelii CS transgene was maintained. Overall, this study demonstrates that the HVR1-modifed Ad vastly improves upon Ad as a promising malaria vaccine platform candidate.

publication date

  • October 2010

has subject area

  • Adenoviridae
  • Animals
  • Antibodies, Protozoan
  • Base Sequence
  • Capsid Proteins
  • Cell Line, Tumor
  • Epitopes, B-Lymphocyte
  • Female
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Plasmodium yoelii
  • Protozoan Proteins

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2947213

Digital Object Identifier (DOI)

  • 10.1172/JCI39812

PubMed ID

  • 20811151

Additional Document Info

start page

  • 3688

end page

  • 3701

volume

  • 120

number

  • 10