Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats

Anna Stedman,Daniel Wright,Lucien Van Keulen,Adrian V S Hill,Sarah C Gilbert,Paul J Wichgers Schreur,George M Warimwe,Bryan Charleston,Jeroen Kortekaas,Madeleine H A Clark,Michael J Francis

doi:10.1038/s41541-019-0138-0

Abstract

Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.

Highlights

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that is endemic to much of Africa and the Arabian Peninsula.[1,2] The virus is transmitted by a wide range of mosquito species[3] and has caused numerous outbreaks since its discovery in Kenya in 1930.4RVFV primarily affects livestock such as sheep, goats, cattle and camels, causing a clinical illness termed Rift Valley fever (RVF) that is characterized by extremely high rates (>90%) of neonatal mortality and abortion in gestating livestock, mainly in sheep and goats.[4]
We previously developed a candidate vaccine, hereafter termed ChAdOx1 RVF, that is based on a replication-deficient simian adenovirus vector (ChAdOx1) encoding the RVFV Gn and Gc glycoproteins.[32]
The mock-vaccinated previously been conducted in pregnant goats, this study group carried 14 foetuses, which were all found dead on necropsy provides a description of RVFV infection in goats during (Supplementary Table 1)

Summary

INTRODUCTION

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that is endemic to much of Africa and the Arabian Peninsula.[1,2] The virus is transmitted by a wide range of mosquito species[3] and has caused numerous outbreaks since its discovery in Kenya in 1930.4. Published in partnership with the Sealy Center for Vaccine Development efficacy in pregnant sheep and goats, as these species suffer the autolysed placenta (Supplementary Table 1). At this point, all greatest burden of mortality, abortion and foetal malformations remaining ewes in this group were euthanised to prevent during RVF outbreaks.[34] As no RVFV challenge study has unnecessary animal discomfort.

RESULTS

DISCUSSION

Findings

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