Safety and efficacy of inactivated African horse sickness (AHS) vaccine formulated with different adjuvants

Piet A Van Rijn,Mieke A Maris-Veldhuis,Miemie Grobler,Isabel M Wright,Baltus J Erasmus,Louis H Maartens,Christiaan A Potgieter

doi:10.1016/j.vaccine.2020.08.072

Abstract

African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae causing African Horse Sickness (AHS) in equids with a mortality of about 95% in naïve horses. AHS causes serious losses in developing countries where horses play a central role in draft power and transportation. There are nine AHSV serotypes inducing no or low cross-neutralizing antibodies. AHSV is spread by biting Culicoides midges. AHS is endemic in sub-Saharan Africa, and a serious threat outside Africa, since Culicoides species in moderate climate conditions are spreading the closely related bluetongue virus. AHS outbreaks will be devastating for the equestrian industry in developed countries. Live-attenuated vaccines (LAVs) are licensed, marketed and in use in Africa. Their application is controversial with regard to safety issues. LAVs are not allowed in AHS-free countries. We here studied inactivated AHSV with different adjuvants in guinea pigs and horses. Subcutaneous and intramuscular vaccination were studied in horses. Local reactions were observed after prime and boost vaccination. In general, neutralizing antibodies (nAbs) titres were very low after prime vaccination, whereas boost vaccination resulted in high nAb titres for some adjuvants. Vaccinated horses were selected based on local reactions and nAb titres to study efficacy. Unfortunately, not all vaccinated horses survived virulent AHSV infection. Further, most survivors temporarily developed clinical signs and viremia. Further, the current prototype inactivated AHS vaccine is not suitable as emergency vaccine, because onset of protection is slow and requires boost vaccinations. On the other hand, inactivated AHS vaccine is completely safe with respect to virus spread, and incorporation of the DIVA principle based on NS3/NS3a serology and exploring a vaccine production platform for other serotypes is feasible. A superior adjuvant increasing the protective response without causing local reactions will be required to develop payable and acceptable inactivated AHS vaccines.

Highlights

African Horse Sickness (AHS) is an OIE listed disease of equids causing mortality up to 95% for naïve horses, while zebras and African donkeys rarely show clinical signs [1,2]
In order to develop inactivated African horse sickness (AHS) vaccines, inactivated AHSV4LP formulated with different adjuvants was studied as prototype vaccine on efficacy and safety with regard to local reactions
Cell culture adapted AHSV4LP was produced on monolayers of Vero cells by serial refreshing of culture medium, and harvests of culture medium were pooled and used as African horse sickness virus (AHSV) antigen

Summary

Introduction

African Horse Sickness (AHS) is an OIE listed disease of equids causing mortality up to 95% for naïve horses, while zebras and African donkeys rarely show clinical signs [1,2]. The causative agent, African horse sickness virus (AHSV), genus Orbivirus, family of Reoviridae, causes different forms of disease ranging from mild fever, subacute and acute infections [3,4,5]. AHS outbreaks lead to huge economic losses by horse deaths, reduction of draft power, and blockade on transportation and trade [6]. AHS is endemic in sub-Saharan Africa but this area could expand by climate change [10,11]. AHS outbreaks are devastating and result in large economic losses in the equestrian industry, and an enormous socio-emotional impact on owners of pet horses. Findings for closely related prototype orbivirus bluetongue virus (BTV) could imply that AHS-free countries in a moderate climate are at risk [19,20,21,22,23]

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Conclusion