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

• Published in: Virology journal Vol. 10; no. 1; p. 349
• Main Authors: Warimwe, George M, Lorenzo, Gema, Lopez-Gil, Elena, Reyes-Sandoval, Arturo, Cottingham, Matthew G, Spencer, Alexandra J, Collins, Katharine A, Dicks, Matthew DJ, Milicic, Anita, Lall, Amar, Furze, Julie, Turner, Alison V, Hill, Adrian VS, Brun, Alejandro, Gilbert, Sarah C
• Format: Journal Article
• Language: English
• Published: England Springer-Verlag 05.12.2013; BioMed Central Ltd; BioMed Central
• Subjects: Adenoviridae - genetics; Adenovirus; Adenoviruses; Analysis; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; CD8-Positive T-Lymphocytes - immunology; Cell culture; clinical trials; Diagnosis; Disease Models, Animal; Drug Carriers; Drug therapy; Female; Fever; Genetic aspects; Genetic Vectors; Glycoproteins; Human adenovirus; Human adenovirus C; human health; human population; humans; immune response; immunization; Influenza; Licenses; Livestock; livestock production; Medical research; Medicine, Experimental; Mice; Mice, Inbred BALB C; Mortality; neutralizing antibodies; Pan troglodytes; pathogens; Peptides; Physiological aspects; Rift Valley fever; Rift Valley Fever - immunology; Rift Valley Fever - prevention & control; Rift Valley fever virus - genetics; Rift Valley fever virus - immunology; T cells; Tuberculosis; Vaccines; 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; viruses; Zoonoses; Kenya; United Kingdom; Europe; Africa
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-10-349

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.