Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever.

George M Warimwe,Sarah C Gilbert,Lopez-Gil Elena,Danny Wright,Vishvanath Nene,Simeon Otieno,Gema Lorenzo,Alejandro Brun,Bryan Charleston,Naif K Alharbi,Kennedy Otingah,Musaad A Al-Dubaib,Edward Okoth,B Veronica Carr,Adrian V S Hill,El-Behiry Ayman,Joseph Gesharisha

doi:10.1038/srep20617

Abstract

Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life-threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A ‘One Health’ vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication-deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication-deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs.

Highlights

Rift Valley Fever virus (RVFV), a negative-stranded RNA virus in the Bunyaviridae family, is listed as an emerging zoonotic Category A viral pathogen in the National Institute for Allergy and Infectious Diseases (NIAID) list of priority pathogens for biodefense research
Whilst the neutralizing antibody titre threshold required for protection against RVFV infection is currently unknown, development of vaccines that elicit antibody titres within the range induced by natural infections is a very attractive way forward
We previously showed that a single-dose immunization with ChAdOx1-GnGc, composed of ChAdOx117,20, a species E adenovirus, encoding RVFV Gn and Gc, elicits high-titre neutralizing antibody and confers protection against lethal viral challenge in mice[24]

Summary

OPEN Chimpanzee Adenovirus Vaccine

Provides Multispecies Protection against Rift Valley Fever received: 23 September 2015 accepted: 08 January 2016. We show that single-dose immunization with ChAdOx1-GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV-neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. ChAd vectors have a large insert capacity (~8 kb), achieve high level, persistent transgene expression and are adaptable for use with diverse immunogens Of relevance to their potential use in a human RVFV vaccine, ChAd vectors, including ChAdOx117, have passed safety evaluations in humans for a wide range of infectious disease targets including malaria[18], HIV19, tuberculosis, influenza[20], hepatitis C21, RSV22 and, most recently, Ebola[23]. We evaluated the immunogenicity of ChAdOx1-GnGc in dromedary camels in Saudi Arabia and compared vaccine-elicited responses to those measured in the sheep, goat and cattle efficacy studies in Kenya

Results and Discussion

Methods

Author Contributions

Additional Information