Additional deletions to further attenuate BA71¿CD2 recombinant virus decreases vaccine efficacy without providing additional safety.

Authors: LOPEZ, ELISABETH - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); BOSCH-CAMOS, LAIA - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); Ramirez-Medina, Elizabeth; VUONO, ELIZABETH - University Of Mississippi; JESUS NAVAS, MARIA - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); ACCENSI, FRANCESC - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); ZHANG, JINYA - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); ALONSO, UXIA - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); ARGILAGUET, JORDI - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); LUISA SALAS, MARIA - University Of Madrid; ANACHKOV, NIKOLAY - University Of Madrid; Gladue, Douglas; Borca, Manuel; PINA-PEDRERO, SONIA - Institute De Recerca I Tecnologia Agroalimentaries (IRTA); RODRIGUEZ, FERNANDO - Institute De Recerca I Tecnologia Agroalimentaries (IRTA)

Submitted to: Viruses
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2021
Publication Date: N/A
Citation: N/A

Interpretive Summary: African swine fever virus (ASFV) causes a devastating disease in swine, called African swine fever (ASF), that is currently spreading across Europe and Asia. There are several experimental vaccines for ASF, however some of them have residual undesirable side effects and require additional genetic changes to increase safety. Here we added two different deletions to a vaccine candidate, however these deletions while not removing the undesirable side effects, decreased the effectiveness of the vaccine.

Technical Abstract: African swine fever (ASF) has become the major threat for global swine industry. Lack of commercial vaccines available complicates the implementation of global control strategies. So far, only live attenuated ASF viruses (ASFV) have demonstrated solid protection efficacy at the experimental level. The implementation of molecular techniques has allowed generating a collection of deletion mutants lacking ASFV specific virulence factors, some of them with promising characteristics as potential vaccines against the pandemic genotype II ASFV strain currently circulating in Africa, Europe, Asia and Oceania. Despite their promising results, there is room for improvement, mainly from the biosafety point of view. Aiming to improve the safety of BA71'CD2f, a cross-protective recombinant LAV lacking the ASFV hemagglutinin (CD2v) available in our laboratory, two double recombinants were generated using BA71'CD2f as template, lacking either the lectin gene (EP153R) or the uridin kinase gene (UK). Comparative in vivo experiments using BA71'CD2f, BA71'CD2DP296R and BA71'CD2EP153R as immunogens demonstrated that deletion of either, DP96R or EP153R from BA71'CD2f, did not reduce increase its safety profile in vivo. Additionally, the protection afforded by the double recombinants viruses was reduced compared with the efficacy obtained with the parental BA71'CD2f. Our results additionally confirm ASFV challenge as the only available method today to evaluate the protective efficacy of any experimental vaccines. We believe that understanding the fine equilibrium between attenuation and inducing protection in vivo deserves further study and might contribute to more rational vaccine designs in the future.