Study reveals promise of plant-based vaccines against African horse sickness

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African Horse Sickness is spread by the Culicoides (midges) species.
African Horse Sickness is spread by the Culicoides (midges) species. Pictured is a 16th-inch-long (1.6mm) female biting midge (Culicoides sonorensis) feeding on blood. © Scott Bauer, USDA ARS

Researchers have taken an important step toward a plant-based vaccine against the African horse sickness virus, generating an immune response in young horses with a formulation targeting more than one serotype.

Daria Rutkowska and her colleagues have reported on their work in developing virus-like particles (VLPs) that can be used as a vaccine. The VLPs were created in Nicotiana benthamiana plants, a close relative of the tobacco plant.

Their work led to the creation of chimeric VLPs, containing structural proteins originating from more than one serotype of African horse sickness. In this case, they generated a chimeric VLP vaccine carrying structural proteins from three different serotypes.

The researchers, writing in the journal BMC Veterinary Research, say their work is the first step toward development of a plant-produced, multivalent AHS vaccine capable of inducing species-specific immunity against all nine AHS serotypes.

African horse sickness is a severe insect-borne viral disease, with a mortality rate of up to 95% in susceptible naïve horses.

The disease is included in the World Organisation for Animal Health (OIE) 2019 list of notifiable animal diseases, resulting in strict quarantine measures governing the export of horses from endemic to non-endemic regions.

This places a significant economic burden on the equine industries in affected countries.

In affected regions, annual vaccination of horses with a commercial live attenuated vaccine is an efficient way of preventing serious losses during the peak season for the disease.

However, there are several drawbacks associated with the use of the current live vaccine, including the risk of reversion to virulence, genome segment reassortment between vaccine and field strains, and problems in pregnant mares.

There is also no way of differentiating between infected and vaccinated animals (DIVA).

“Thus there is an urgent need for safe, efficacious and cost-effective new generation vaccines against African horse sickness for use in endemic as well as non-endemic countries,” the study team said.

This, they say, is why alternative safe and effective vaccination strategies such as VLPs are being investigated.

VLPs are considered a safe and effective alternative to live attenuated vaccines for many viral diseases.

These self-assembling particles, composed of viral structural proteins but lacking the viral genome, are of similar size and shape to viruses but are unable to replicate. They do not contain a genome and are DIVA-compliant due to their lack of non-structural proteins.

The researchers described their work with Nicotiana benthamiana dXT/FT plants, and how their insertion of viral proteins not only allowed for the assembly of homogenous AHSV-1 VLPs but also single, double and triple chimeric VLPs.

They reported that their triple chimeric AHSV-6/AHSV-3/AHSV-1 VLP proved stable. It was purified and proved to be safe and immunogenic in six-month-old foals.

They also tested their plant-produced monovalent AHSV-6 VLPs in young horses. It proved safe and was found to generate a weak neutralizing immune response against homologous AHSV virus.

The immune response was similar to that from the AHSV-6 monovalent live attenuated vaccine.

These results are not unexpected, they say, as previous studies have shown that young foals vaccinated with the commercial polyvalent, as well as monovalent AHSV vaccines, have weak or non-detectable and variable antibody responses to all AHSV serotypes, except serotype 1.

Some only seroconvert after revaccination.

Current protocols with the live attenuated vaccine recommend 2 to 3 vaccinations to obtain sufficient antibodies to confer protection against all serotypes in the vaccine, and a recent study suggested up to eight vaccinations before full protection can be conferred.

“It is likely that, as with the live attenuated polyvalent vaccine, multiple vaccinations with the AHSV VLPs will be required to induce titres of neutralizing antibodies sufficient for protection.”

As AHS has nine serotypes, it would be necessary to assemble VLPs of all nine serotypes and combine them into a multivalent vaccine in order to protect horses against the disease, they say.

The full study team comprised Rutkowska, Tsepo Tsekoa, and Martha O’Kennedy, from CSIR Chemicals in Pretoria, South Africa; and Nobalanda Mokoena and Vusi Dibakwane, from Onderstepoort Biological Products SOC Ltd, in Onderstepoort, South Africa.

Rutkowska, D.A., Mokoena, N.B., Tsekoa, T.L. et al. Plant-produced chimeric virus-like particles – a new generation vaccine against African horse sickness. BMC Vet Res 15, 432 (2019) doi:10.1186/s12917-019-2184-2

The study, published under a Creative Commons License, can be read here

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