Development of a dual vaccine against East Coast fever and lumpy skin disease

Leah Whittle; Ros Chapman; Nicola Douglass; Mohamed Jaffer; Emmanuel Margolin; Edward Rybicki; Anna-Lise Williamson

doi:10.3389/fimmu.2023.1143034

Development of a dual vaccine against East Coast fever and lumpy skin disease

Front Immunol. 2023 Mar 30:14:1143034. doi: 10.3389/fimmu.2023.1143034. eCollection 2023.

Authors

Leah Whittle^{1

2}, Ros Chapman^{1

2}, Nicola Douglass^{1

2}, Mohamed Jaffer³, Emmanuel Margolin^{1

2

4}, Edward Rybicki^{1

4}, Anna-Lise Williamson^{1

2}

Affiliations

¹ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
² Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
³ Electron Microscope Unit, University of Cape Town, Cape Town, South Africa.
⁴ Biopharming Research Unit, Department of Molecular and Cell Biology, Faculty of Science, University of Cape Town, Cape Town, South Africa.

Abstract

East Coast fever is an acute bovine disease caused by the apicomplexan parasite Theileria parva and is regarded as one of the most important tick-vectored diseases in Africa. The current vaccination procedure has many drawbacks, as it involves the use of live T. parva sporozoites. As a novel vaccination strategy, we have constructed the recombinant lumpy skin disease virus (LSDV) named LSDV-SODis-p67HA-BLV-Gag, encoding a modified form of the T. parva p67 surface antigen (p67HA), as well as the bovine leukemia virus (BLV) gag gene for the formation of virus-like particles (VLPs) to potentially enhance p67 immunogenicity. In place of the native sequence, the chimeric p67HA antigen has the human tissue plasminogen activator signal sequence and the influenza hemagglutinin A2 transmembrane domain and cytoplasmic tail. p67HA was detected on the surface of infected cells, and VLPs comprising BLV Gag and p67HA were produced. We also show that higher multiple bands observed in western blot analysis are due to glycosylation of p67. The two vaccines, pMExT-p67HA (DNA) and LSDV-SODis-p67HA-BLV-Gag, were tested for immunogenicity in mice. p67-binding antibodies were produced by vaccinated animals, with higher titers detected in mice vaccinated with the recombinant LSDV. This candidate dual vaccine warrants further testing in cattle.

Keywords: East Coast fever; Gag; LSDV; Theileria parva; VLPs; p67; poxvirus; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cattle
Humans
Lumpy Skin Disease* / prevention & control
Mice
Protozoan Proteins
Protozoan Vaccines*
Theileriasis* / parasitology
Theileriasis* / prevention & control
Tissue Plasminogen Activator

Substances

Tissue Plasminogen Activator
Protozoan Proteins
Protozoan Vaccines

Grants and funding

This work is based on the research supported in part by the National Research Foundation of South Africa (Grant Numbers 64815 and 138792) and the Poliomyelitis Research Foundation (Grant Number 19/85).