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

Virology Journal

Sarah C Gilbert²  Alejandro Brun¹  Adrian VS Hill²  Alison V Turner²  Julie Furze²  Amar Lall²  Anita Milicic²  Matthew DJ Dicks²  Katharine A Collins²  Alexandra J Spencer²  Matthew G Cottingham²  Arturo Reyes-Sandoval²  Elena Lopez-Gil¹  Gema Lorenzo¹  George M Warimwe² 

[1] Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain;The Jenner Institute, University of Oxford, Oxford, UK

关键词: Vaccine;    Adenovirus vector;    Rift Valley Fever;   

Others  :  820085
DOI  :  10.1186/1743-422X-10-349

 received in 2013-10-09, accepted in 2013-11-29,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Warimwe et al.; licensee BioMed Central Ltd.

【 图 表 】

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