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Identification and Characterization of African Swine Fever Virus Proteins and Their Contribution to Protection
Identification and Characterization of African Swine Fever Virus Proteins and Their Contribution to Protection
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152021
- ISBN
- 9798384049173
- DDC
- 576.6
- 서명/저자
- Identification and Characterization of African Swine Fever Virus Proteins and Their Contribution to Protection
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 189 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-03, Section: A.
- 주기사항
- Advisor: Diel, Diego.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약African Swine Fever Virus (ASFV) is the causative agent of African swine fever, a transboundary disease of swine, with morbidity and mortality rates of up to 100%. The virus encodes for at least 150 proteins and can be transmitted by soft ticks, direct contact or by fomites and transit of vehicles and personnel between farms. Currently, there are a limited number of live attenuated vaccines commercially available for ASFV, and the main obstacle to vaccine development is the poor understanding of the virus' protective antigens. In this study, we generated a library of ten recombinant vesicular stomatitis virus (VSV) and seven recombinant Orf virus (rORFV) encoding different ASFV proteins. Two animal experiments were conducted to evaluate the safety and efficacy of the recombinant viruses as ASFV vaccine candidates. In study 1, piglets were immunized with ten rVSV. Rectal temperatures of vaccinated animals did not increase post immunization, and no adverse reaction to the vaccine candidates was observed. At day 56 post vaccination, animals were challenged with the highly virulent ASFV strain Armenia 07 (Arm07). Both groups of animals presented with fever following vaccination, and there was no difference in clinicals signs and viremia between the groups. By 12 dpc, all animals died. In study 2, piglets were immunized with a cocktail of seven rORFV and three rVSV at 0 dpv, boosted with ten rVSV at 21 dpv, and again with seven rORFV and three rVSV at 35 dpv. At 56 dpv, all animals were challenged with ASFV Arm07. Overall, the rectal temperatures of vaccinated animals did not increase above the normal range, while control animals presented with high temperatures. Similarly, control animals showed higher clinical scores and higher viremia levels than vaccinated pigs. Additionally, all control animals died by 14 dpc, while 50% of vaccinated animals survived until the end of the experiment on day 15 pc. These results show that the prime-boost rORFV-rVSV-rORFV strategy resulted in lower disease severity and lower viremia titers in vaccinated animals and provided partial protection against ASFV challenge. In an additional study, we sought to characterize the immunogenicity of four ASFV proteins. For this, pigs were immunized with ORFV recombinants encoding ASFV genes B602L, CP204L, E184L and I73R. ELISA assays showed that the animals produced high antibody titers against ASFV p30, encoded by gene CP204L. We decided to focus on the characterization of this highly immunogenic protein of ASFV. We identified an immunodominant B-cell epitope of 12 amino acids of length (113-NECTSSFETLFE-124) withing the exposed loop of ASFV p30. Sequence analysis showed this epitope is highly conserved among the various ASFV genotypes, making it a good candidate for a DIVA vaccine marker. Characterization of p30-directed antibodies demonstrated that they induce antibody dependent cell cytotoxicity (ADCC) and could contribute to clearance of ASFV infected cells. The results of our study provide important insights for the generation of safe and effective ASFV vaccines and contribute to the better understanding of the role of the ASFV p30 in viral immunity.
- 일반주제명
- Virology
- 일반주제명
- Public health
- 일반주제명
- African studies
- 일반주제명
- Biochemistry
- 일반주제명
- Immunology
- 키워드
- ADCC
- 키워드
- DIVA vaccine
- 기타저자
- Cornell University Biomedical and Biological Sciences
- 기본자료저록
- Dissertations Abstracts International. 86-03A.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798384049173
■035 ▼a(MiAaPQ)AAI31332292
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a576.6
■1001 ▼aGomes Noll, Jessica Caroline.▼0(orcid)0000-0001-5693-6957
■24510▼aIdentification and Characterization of African Swine Fever Virus Proteins and Their Contribution to Protection
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a189 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-03, Section: A.
■500 ▼aAdvisor: Diel, Diego.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aAfrican Swine Fever Virus (ASFV) is the causative agent of African swine fever, a transboundary disease of swine, with morbidity and mortality rates of up to 100%. The virus encodes for at least 150 proteins and can be transmitted by soft ticks, direct contact or by fomites and transit of vehicles and personnel between farms. Currently, there are a limited number of live attenuated vaccines commercially available for ASFV, and the main obstacle to vaccine development is the poor understanding of the virus' protective antigens. In this study, we generated a library of ten recombinant vesicular stomatitis virus (VSV) and seven recombinant Orf virus (rORFV) encoding different ASFV proteins. Two animal experiments were conducted to evaluate the safety and efficacy of the recombinant viruses as ASFV vaccine candidates. In study 1, piglets were immunized with ten rVSV. Rectal temperatures of vaccinated animals did not increase post immunization, and no adverse reaction to the vaccine candidates was observed. At day 56 post vaccination, animals were challenged with the highly virulent ASFV strain Armenia 07 (Arm07). Both groups of animals presented with fever following vaccination, and there was no difference in clinicals signs and viremia between the groups. By 12 dpc, all animals died. In study 2, piglets were immunized with a cocktail of seven rORFV and three rVSV at 0 dpv, boosted with ten rVSV at 21 dpv, and again with seven rORFV and three rVSV at 35 dpv. At 56 dpv, all animals were challenged with ASFV Arm07. Overall, the rectal temperatures of vaccinated animals did not increase above the normal range, while control animals presented with high temperatures. Similarly, control animals showed higher clinical scores and higher viremia levels than vaccinated pigs. Additionally, all control animals died by 14 dpc, while 50% of vaccinated animals survived until the end of the experiment on day 15 pc. These results show that the prime-boost rORFV-rVSV-rORFV strategy resulted in lower disease severity and lower viremia titers in vaccinated animals and provided partial protection against ASFV challenge. In an additional study, we sought to characterize the immunogenicity of four ASFV proteins. For this, pigs were immunized with ORFV recombinants encoding ASFV genes B602L, CP204L, E184L and I73R. ELISA assays showed that the animals produced high antibody titers against ASFV p30, encoded by gene CP204L. We decided to focus on the characterization of this highly immunogenic protein of ASFV. We identified an immunodominant B-cell epitope of 12 amino acids of length (113-NECTSSFETLFE-124) withing the exposed loop of ASFV p30. Sequence analysis showed this epitope is highly conserved among the various ASFV genotypes, making it a good candidate for a DIVA vaccine marker. Characterization of p30-directed antibodies demonstrated that they induce antibody dependent cell cytotoxicity (ADCC) and could contribute to clearance of ASFV infected cells. The results of our study provide important insights for the generation of safe and effective ASFV vaccines and contribute to the better understanding of the role of the ASFV p30 in viral immunity.
■590 ▼aSchool code: 0058.
■650 4▼aVirology
■650 4▼aPublic health
■650 4▼aAfrican studies
■650 4▼aBiochemistry
■650 4▼aImmunology
■653 ▼aADCC
■653 ▼aAfrican Swine Fever Virus
■653 ▼aAntibody-dependent cell cytotoxicity
■653 ▼aDIVA vaccine
■653 ▼aProtein characterization
■690 ▼a0720
■690 ▼a0982
■690 ▼a0487
■690 ▼a0293
■690 ▼a0573
■71020▼aCornell University▼bBiomedical and Biological Sciences.
■7730 ▼tDissertations Abstracts International▼g86-03A.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17162511▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
