Identification of African swine fever virus antigens for development of an efficacious subunit vaccine

dc.contributor.authorZajac, Michelle Dawn
dc.date.accessioned2023-04-11T19:32:45Z
dc.date.available2023-04-11T19:32:45Z
dc.date.graduationmonthMay
dc.date.issued2023
dc.description.abstractAfrican Swine Fever (ASF) is a virulent disease in domestic swine and wild boar that is caused by the African Swine Fever Virus (ASFV), a complex enveloped DNA virus in the family Asfarviridae. Epidemics caused by the ASFV have an overwhelming economic influence on impacted areas and jeopardize swine commerce globally with nearly 100% mortality in naïve populations. There is no vaccine or treatment available and current control measures focus on the use of antiquated regulatory methods such as quarantine, limiting transport, and depopulation of affected swine. Previous studies have shown that some ASFV mutants can confer protection, but safety and vaccine virus scale-up need to be addressed. Development of a subunit vaccine would be more attractive: however, the actual protective antigen(s) have not yet been identified. The first study aimed to identify ASFV subunit vaccine candidates that contain CD8+ T cell epitopes by using lymphocytes from pigs that had been immunized with an antigen cocktail, which included the largest ASFV protein (pp220 polyprotein) that is processed to generate p5, p34, p14, p37, and p150 individual proteins. The results from this study showed that four predicted SLA-I binding nonamer peptides (p34¹⁶¹ˉ¹⁶⁹, p37⁸⁵⁹ˉ⁸⁶⁷, p150¹³⁶³ˉ¹³⁷¹, and p150¹⁴⁶³ˉ¹⁴⁷¹) elicited robust IFN-[gamma]+ responses in peripheral blood mononuclear cells (PBMCs) and splenocytes. These peptides are highly conserved among different ASFV genomes. The role played by these epitopes in immune protection will need to be determined in challenge studies. In the second study, an adjuvanted or non-adjuvanted adenovirus-based subunit vaccine candidate containing nearly all of the proteins in the ASFV proteome (which included pp220 antigens) was evaluated in pigs in a homologous prime-boost-boost immunization regimen followed by challenge using a natural transmission model. The results of this second study showed that this adenovirus-vectored ASFV vaccine cocktail induced robust antibody responses in swine, but only one pig survived. Future studies will entail the development of a porcine-specific granzyme B (PGB) monoclonal antibody to screen PBMCs from immunized pigs to identify novel IFN-[gamma]+/granzyme B+ T cell epitopes present in ASFV vaccine candidates by using flow cytometric analyses following intracellular staining. More screening is required to identify additional novel IFN-[gamma]+/granzyme B+ T cell epitopes for inclusion in a rationally designed prototype subunit vaccine to be tested for protective efficacy in pigs. Altogether, the knowledge generated in these and future studies will inform the design of an efficacious ASFV subunit vaccine that is needed to safeguard the pork industry against the risk posed by ASFV.
dc.description.advisorWaithaka Mwangi
dc.description.degreeDoctor of Philosophy
dc.description.departmentDepartment of Diagnostic Medicine/Pathobiology
dc.description.levelDoctoral
dc.description.sponsorshipUSDA National Institute of Food and Agriculture; Broad Agency Agreement with the Science and Technology Directorate of the United States Department of Homeland Security; United States Department of Agriculture Animal Plant Health Inspection Service's National Bio- and Agro-defense Facility Scientist Training Program
dc.identifier.urihttps://hdl.handle.net/2097/42983
dc.language.isoen_US
dc.publisherKansas State University
dc.rights.uri© the author. This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectAfrican swine fever virus
dc.subjectIgG
dc.subjectIFN-gamma
dc.subjectCTL
dc.subjectSLA-I
dc.subjectSubunit vaccine
dc.titleIdentification of African swine fever virus antigens for development of an efficacious subunit vaccine
dc.typeDissertation

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