Deciphering the onset of cross protection conferred by the vaccine prototype BA71ΔCD2 against african swine fever

African swine fever (ASF) is a pandemic viral disease harmless to humans but causing high mortality in domestic and wild pigs. Although it has been eradicated from Spain since 1994, it continues to cause severe economic losses in the pig meat sector in several countries in Eastern Europe, Asia, sub-Saharan Africa and the Caribbean. During 2018-2019, almost 25% of domestic pigs worldwide died from the disease, keeping ASF on the podium as the most relevant swine disease. Given that there is no commercial vaccine available globally, the reintroduction or spread of the virus in ASF-free areas is a constant threat.

In 2023, the first live attenuated vaccine (LAV) against ASF was approved for use and marketing only in Vietnam. Attenuated vaccines are vaccines that contain less virulent strains of the pathogen in question, either because they have been genetically modified or because of the characteristics of the selected strain. Although their use is controversial due to the associated biosecurity risks, LAVs are currently the only vaccines that have been successful in generating a sufficiently robust immune response in pigs to protect them against the disease. The African swine fever research group at IRTA-CReSA, led by Dr Fernando Rodríguez and Dr Jordi Argilaguet, developed a LAV called BA71ΔCD2 in 2017. The vaccine prototype is based on a strain of ASF genotype Y isolated in Spain in 1971 from which the gene expressing the viral haemagglutinin CD2v has been deleted. Intranasal inoculation of this vaccine prototype has been shown to be effective in developing heterologous protection against strains belonging to the two genotypes circulating in Asia and Europe, a unique feature compared to other vaccines developed so far. Although the group’s previous studies have already demonstrated the vaccine’s efficacy from 21 days after administration, it remained to be concluded what minimum time period is necessary for the development of animal protection and to determine which immunological mechanisms are associated with it.

To answer these questions, we conducted a study with three groups of pigs vaccinated with BA71ΔCD2 on different days (3, 7 and 12) before being infected with a lethal strain of ASF virus, while a fourth group of animals was left unvaccinated as a control for disease development. What we observed was that vaccination 7 days or less prior to infection with the virus did not provide sufficient time for the animal to develop a sufficient immune response to control the infection, although it did result in a delay in the course of the disease proportional to the time post-vaccination. In contrast, vaccination 12 days prior to infection was shown to control both the fever associated with the acute phase of ASF, systemic viraemia and virus shedding. Evaluation of organs and tissues during necropsy of the animals also revealed significant differences in the severity of ASF-associated lesions between the group vaccinated 12 days before and the groups vaccinated 7 and 3 days before, being much more evident in the latter groups. Looking at the immune status of the animals in the different groups, we observed that the protection shown by the group vaccinated 12 days before was associated with the appearance of a humoral response and the presence of a cytotoxic response – mostly to natural killer (NK) cells and T lymphocytes – at the time of infection with ASFV. The results obtained in this study are in line with those previously obtained in animals vaccinated three weeks prior to infection, suggesting that 12 days after vaccination with BA71ΔCD2, animals are endowed with a sufficiently robust immune context to cope with ASF.

The study concludes that protection against ASF primarily requires mechanisms inherent to the adaptive response, and demonstrates that the attenuated BA71ΔCD2 vaccine can confer protective immunity from 12 days post-vaccination, information that may prove crucial in the face of an ASF outbreak that relies on rapid and effective emergency action.

Authors of the work: David Marín Moraleda, Jordana Muñoz Basagoiti, Aida Tort Miró, Mª Jesús Navas, Marta Muñoz, Enric Vidal, Àlex Cobos, Beatriz Martín Mur, Sochanwattey Meas, Veronika Motuzova, Chia-Yu Chang, Marta Gut, Francesc Accensi, Sonia Pina Pedrero, José Ignacio Núñez, Anna Esteve Codina, Boris Gavrilov, Fernando Rodríguez, Lihong Liu and Jordi Argilaguet.

Link to the article: https://doi.org/10.3390/vaccines12050517

This work has been funded by Ministerio Español de Ciencia e Innovación

(MICIU/AEI/10.13039/501100011033, beca PID2022-136312OB-I00)

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