Abstract

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1.The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1.Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain.

Highlights

  • Malignant catarrhal fever (MCF) is a usually-fatal lymphoproliferative disease affecting a range of ungulates caused by members of the Macavirus genus of gammaherpesviruses, alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2) [1,2,3]

  • We show that the attenuated AlHV-1 MCF vaccine requires an adjuvant to induce optimal immune responses but the virus need not be viable

  • In order to study longer-term vaccine virus stability when formulated with adjuvant, aliquots of attenuated AlHV-1 were incubated in the presence or absence of Emulsigen (20%) with daily mixing for up to two months

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Summary

Introduction

Malignant catarrhal fever (MCF) is a usually-fatal lymphoproliferative disease affecting a range of ungulates caused by members of the Macavirus genus of gammaherpesviruses, alcelaphine herpesvirus 1 (AlHV-1) and ovine herpesvirus 2 (OvHV-2) [1,2,3]. AlHV-1 is carried asymptomatically by wildebeest but can be transmitted to disease-susceptible ungulates causing significant losses in areas of eastern and southern Africa where wildebeest and livestock come into contact and in zoological collections. MCF does not appear to transmit horizontally between affected animals, suggesting clinical disease occurs only in dead-end hosts, but examples of vertical transmission in MCF reservoir and susceptible species have been recorded [6,7,8]. OvHV2 is carried asymptomatically by sheep and sheep-associated (SA-) MCF is a problem worldwide wherever reservoir and diseasesusceptible hosts cohabit. MCF has both economic and animal welfare impacts [2,9,10,11,12]

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