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

Journal article

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: Warimwe, G; Lorenzo, G; Lopez-Gil, E; Reyes-Sandoval, A; Cottingham, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Virology journal
• Volume: 10
• Issue: 1
• Pages: 349
• Publication date: 2013-01-01
• DOI: 10.1186/1743-422x-10-349
• EISSN: 1743-422X
• ISSN: 1743-422X
• Language: English
• Keywords: Antibodies, Neutralizing; Viral Vaccines; Disease Models, Animal; Vaccines, Synthetic; Rift Valley Fever; Mice, Inbred BALB C; Animals; Rift Valley fever virus; Antibodies, Viral; Vaccines, Attenuated; Mice; Female; Adenoviridae; CD8-Positive T-Lymphocytes; Genetic Vectors; Drug Carriers