title: Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice.
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.
authors.affiliation: The Jenner Institute, University of Oxford, Oxford, UK. george.warimwe@ndm.ox.ac.uk.
authors.forename: George M
authors.initials: GM
authors.lastname: Warimwe
authors.forename: Gema
authors.initials: G
authors.lastname: Lorenzo
authors.forename: Elena
authors.initials: E
authors.lastname: Lopez-Gil
authors.forename: Arturo
authors.initials: A
authors.lastname: Reyes-Sandoval
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Cottingham
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Collins
authors.forename: Matthew D J
authors.initials: MD
authors.lastname: Dicks
authors.forename: Anita
authors.initials: A
authors.lastname: Milicic
authors.forename: Amar
authors.initials: A
authors.lastname: Lall
authors.forename: Julie
authors.initials: J
authors.lastname: Furze
authors.forename: Alison V
authors.initials: AV
authors.lastname: Turner
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Alejandro
authors.initials: A
authors.lastname: Brun
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D012295:Rift Valley Fever / Q000276:immunology / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014765:Viral Vaccines