COMPARATIVE ANALYSIS OF NATURALLY ACQUIRED AND VACCINE INDUCED RIFT VALLEY FEVER ANTIBODY LEVELS IN LIVESTOC

Abstract

Rift Valley Fever (RVF) is a viral zoonosis that is spread by mosquitoes and majorly affects livestock causing high abortion rates among gestating animals and death in neonates. However, the disease can spill over to humans causing mild and self-limiting conditions that has potential to cause severe disease with high case fatality. Protective virus neutralizing antibodies (nAbs) directed towards the virus surface glycoproteins Gn and Gc are induced through natural RVF infection or by vaccination. Understanding the long-lived naturally acquired immunity to RVF can help inform vaccine development. Licensed vaccines based on RVF virus attenuation and inactivation are commercially available for veterinary use. However, these have some safety concerns including residual pathogenicity that results in abortion and fetal abnormalities when pregnant animals are immunized. Vaccines based on RVF virus inactivation require multiple dosing to generate protective immune response for an extended duration. A non-replicating chimpanzee adenovirus vectored RVF vaccine (ChAdOx1 RVF) which addresses these concerns is in development. ChAdOx1 RVF has been shown to have good safety profile and highly protective in goats, sheep and cattle in viral challenge studies (including during pregnancy). Because nAbs are associated with protection, it is plausible that induction of similar antibodies within the range elicited by natural exposure could be a marker of protective immunity. In this project, I sought to answer the question of whether antibodies induced by ChAdOx1 RVF vaccination are within the range elicited by natural RVF exposure in livestock. To answer this question, I measured binding IgG responses by Enzyme-Linked Immunosorbent Assay (ELISA) and nAbs by focus reduction neutralization test (FRNT). The analysis of results demonstrated that ChAdOx1 RVF can induce binding IgG and nAbs that are within the levels induced by natural infection across the species. A positive correlation was observed between binding IgG and nAbs except in vaccinated cattle. These findings are useful in predicting ChAdOx1 RVF vaccine performance supporting its further development for use to counter RVF epidemics