Deletion of E184L, a Putative DIVA Target from the Pandemic Strain of African Swine Fever Virus, Produces a Reduction in Virulence and Protection against Virulent Challenge
Autor/a
Ramirez-Medina, Elizabeth
Vuono, Elizabeth
Rai, Ayushi
Pruitt, Sarah
Espinoza, Nallely
Velazquez-Salinas, Lauro
Zhu, James
Borca, Manuel V.
Gladue, Douglas P.
Fecha de publicación
2022-01-12ISSN
0022-538X
Resumen
African swine fever (ASF) is currently causing a major pandemic affecting the swine industry and protein availability from Central Europe to East and South Asia. No commercial vaccines are available, making disease control dependent on the elimination of affected animals. Here, we show that the deletion of the African swine fever virus (ASFV) E184L gene from the highly virulent ASFV Georgia 2010 (ASFV-G) isolate produces a reduction in virus virulence during the infection in swine. Of domestic pigs intramuscularly inoculated with a recombinant virus lacking the E184L gene (ASFV-G-ΔE184L), 40% experienced a significantly (5 days) delayed presentation of clinical disease and, overall, had a 60% rate of survival compared to animals inoculated with the virulent parental ASFV-G. Importantly, all animals surviving ASFV-G-ΔE184L infection developed a strong antibody response and were protected when challenged with ASFV-G. As expected, a pool of sera from ASFV-G-ΔE184L-inoculated animals lacked any detectable antibody response to peptides partially representing the E184L protein, while sera from animals inoculated with an efficacious vaccine candidate, ASFV-G-ΔMGF, strongly recognize the same set of peptides. These results support the potential use of the E184L deletion for the development of vaccines able to differentiate infected from vaccinated animals (DIVA). Therefore, it is shown here that the E184L gene is a novel ASFV determinant of virulence that can potentially be used to increase safety in preexisting vaccine candidates, as well as to provide them with DIVA capabilities. To our knowledge, E184L is the first ASFV gene product experimentally shown to be a functional DIVA antigenic marker.
IMPORTANCE No commercial vaccines are available to prevent African swine fever (ASF). The ASF pandemic caused by the ASF virus Georgia 2010 (ASFV-G) strain is seriously affecting pork production in a contiguous geographical area from Central Europe to East Asia. The only effective experimental vaccines are viruses attenuated by deleting ASFV genes associated with virus virulence. Therefore, identification of such genes is of critical importance for vaccine development. Here, we report the discovery of a novel determinant of ASFV virulence, the E184L gene. Deletion of the E184L gene from the ASFV-G genome (ASFV-G-ΔE184L) produced a reduction in virus virulence, and importantly, animals surviving infection with ASFV-G-ΔE184L were protected from developing ASF after challenge with the virulent parental virus ASFV-G. Importantly, the virus protein encoded by E184L is highly immunogenic, making a virus lacking this gene a vaccine candidate that allows the differentiation of infected from vaccinated animals (DIVA). Here, we show that unlike what is observed in animals inoculated with the vaccine candidate ASFV-G-ΔMGF, ASFV-G-ΔE184L-inoculated animals do not mount a E184L-specific antibody response, indicating the feasibility of using the E184L deletion as the antigenic marker for the development of a DIVA vaccine in ASFV.
Tipo de documento
Artículo
Versión del documento
Versión aceptada
Lengua
English
Materias (CDU)
619 - Veterinaria
Páginas
42
Publicado por
American Society for Microbiology
Publicado en
Journal of Virology
Citación
Ramirez-Medina, Elizabeth, Elizabeth Vuono, Ayushi Rai, Sarah Pruitt, Nallely Espinoza, Lauro Velazquez-Salinas, Sonia Pina-Pedrero, James Zhu, Fernando Rodriguez, Manuel V. Borca, and Douglas P.Gladue. 2022. "Deletion of E184L, a Putative DIVA Target from the Pandemic Strain of African Swine Fever Virus, Produces a Reduction in Virulence and Protection against Virulent Challenge". Journal Of Virology 96 (1). doi:10.1128/jvi.01419-21.
Número del acuerdo de la subvención
MICIU/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2019-107616RB-I00/ES/Peste porcina africana; de la emergencia a evitar el endemismo/
Program
Sanitat Animal
Este ítem aparece en la(s) siguiente(s) colección(ones)
- ARTICLES CIENTÍFICS [2829]
Derechos
Copyright © 2022 American Society for Microbiology