Open Access Highly Accessed Research

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

George M Warimwe1*, Gema Lorenzo2, Elena Lopez-Gil2, Arturo Reyes-Sandoval1, Matthew G Cottingham1, Alexandra J Spencer1, Katharine A Collins1, Matthew DJ Dicks1, Anita Milicic1, Amar Lall1, Julie Furze1, Alison V Turner1, Adrian VS Hill1, Alejandro Brun2 and Sarah C Gilbert1

Author Affiliations

1 The Jenner Institute, University of Oxford, Oxford, UK

2 Centro de Investigación en Sanidad Animal, Instituto Nacional de Investigación Agraria y Alimentaria, Valdeolmos, Madrid, Spain

For all author emails, please log on.

Virology Journal 2013, 10:349  doi:10.1186/1743-422X-10-349

Published: 5 December 2013

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.

Keywords:
Rift Valley Fever; Adenovirus vector; Vaccine