Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice

Virol J. 2013 Dec 5:10:349. doi: 10.1186/1743-422X-10-349.

Abstract

Background: Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.

Methods: Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.

Results: A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.

Conclusions: Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Models, Animal
  • Drug Carriers*
  • Female
  • Genetic Vectors*
  • Mice
  • Mice, Inbred BALB C
  • Rift Valley Fever / immunology
  • Rift Valley Fever / prevention & control*
  • Rift Valley fever virus / genetics
  • Rift Valley fever virus / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Drug Carriers
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • Viral Vaccines