The Presence of Virus Neutralizing Antibodies Is Highly Associated with Protection against Virulent Challenge in Domestic Pigs Immunized with ASFV live Attenuated Vaccine Candidates
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Virus Neutralization Stock
2.2. Neutralization Assay
2.3. Detection of ASFV Specific Antibody Response by ELISA
2.4. Animal Study Design
2.5. Statistical Analysis
3. Results and Discussion
3.1. Association between the Presence of ASFV Specific Antibodies Detected by ELISA and Protection against the Virulent Challenge in Pigs Immunized with Live Attenuated Vaccine Candidates
3.2. Detection of Virus Neutralizing Antibodies in Pigs Immunized with Live Attenuated Vaccine Candidates
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Costard, S.; Wieland, B.; de Glanville, W.; Jori, F.; Rowlands, R.; Vosloo, W.; Roger, F.; Pfeiffer, D.U.; Dixon, L.K. African swine fever: How can global spread be prevented? Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009, 364, 2683–2696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tran, X.H.; Phuong, L.; Huy, N.Q.; Thuy, D.T.; Nguyen, V.D.; Quang, P.H.; Ngôn, Q.V.; Rai, A.; Gay, C.G.; Gladue, D.P.; et al. Evaluation of the Safety Profile of the ASFV Vaccine Candidate ASFV-G-ΔI177L. Viruses 2022, 14, 896. [Google Scholar] [CrossRef] [PubMed]
- Tran, X.H.; Le, T.; Nguyen, Q.H.; Do, T.T.; Nguyen, V.D.; Gay, C.G.; Borca, M.V.; Gladue, D.P. African swine fever virus vaccine candidate ASFV-G-ΔI177L efficiently protects European and native pig breeds against circulating Vietnamese field strain. Transbound Emerg. Dis. 2022, 69, e497–e504. [Google Scholar] [CrossRef] [PubMed]
- O’Donnell, V.; Risatti, G.R.; Holinka, L.G.; Krug, P.W.; Carlson, J.; Velazquez-Salinas, L.; Azzinaro, P.A.; Gladue, D.P.; Borca, M.V. Simultaneous Deletion of the 9GL and UK Genes from the African Swine Fever Virus Georgia 2007 Isolate Offers Increased Safety and Protection against Homologous Challenge. J. Virol. 2016, 91, e01760-16. [Google Scholar] [CrossRef] [Green Version]
- O’Donnell, V.; Holinka, L.G.; Krug, P.W.; Gladue, D.P.; Carlson, J.; Sanford, B.; Alfano, M.; Kramer, E.; Lu, Z.; Arzt, J.; et al. African Swine Fever Virus Georgia 2007 with a Deletion of Virulence-Associated Gene 9GL (B119L), when Administered at Low Doses, Leads to Virus Attenuation in Swine and Induces an Effective Protection against Homologous Challenge. J. Virol. 2015, 89, 8556–8566. [Google Scholar] [CrossRef] [Green Version]
- O’Donnell, V.; Holinka, L.G.; Gladue, D.P.; Sanford, B.; Krug, P.W.; Lu, X.; Arzt, J.; Reese, B.; Carrillo, C.; Risatti, G.R.; et al. African Swine Fever Virus Georgia Isolate Harboring Deletions of MGF360 and MGF505 Genes Is Attenuated in Swine and Confers Protection against Challenge with Virulent Parental Virus. J. Virol. 2015, 89, 6048–6056. [Google Scholar] [CrossRef] [Green Version]
- Chen, W.; Zhao, D.; He, X.; Liu, R.; Wang, Z.; Zhang, X.; Li, F.; Shan, D.; Chen, H.; Zhang, J.; et al. A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs. Sci. China Life Sci. 2020, 63, 623–634. [Google Scholar] [CrossRef]
- Borca, M.V.; Ramirez-Medina, E.; Silva, E.; Vuono, E.; Rai, A.; Pruitt, S.; Holinka, L.G.; Velazquez-Salinas, L.; Zhu, J.; Gladue, D.P. Development of a Highly Effective African Swine Fever Virus Vaccine by Deletion of the I177L Gene Results in Sterile Immunity against the Current Epidemic Eurasia Strain. J. Virol. 2020, 94, e02017-19. [Google Scholar] [CrossRef]
- Montoya, M.; Franzoni, G.; Pérez-Nuñez, D.; Revilla, Y.; Galindo, I.; Alonso, C.; Netherton, C.L.; Blohm, U. 3. Immune Responses against African Swine Fever Virus Infection. In Understanding and Combatting African Swine Fever; Wageningen Academic Publishers: Wageningen, The Netherlands, 2021; pp. 63–85. [Google Scholar] [CrossRef]
- Martins, C.L.; Leitão, A.C. Porcine immune responses to African swine fever virus (ASFV) infection. Vet. Immunol. Immunopathol. 1994, 43, 99–106. [Google Scholar] [CrossRef]
- Sánchez-Cordón, P.J.; Jabbar, T.; Chapman, D.; Dixon, L.K.; Montoya, M. Absence of Long-Term Protection in Domestic Pigs Immunized with Attenuated African Swine Fever Virus Isolate OURT88/3 or BeninΔMGF Correlates with Increased Levels of Regulatory T Cells and Interleukin-10. J. Virol. 2020, 94, e00350-20. [Google Scholar] [CrossRef]
- Oura, C.; Denyer, M.S.; Takamatsu, H.; Parkhouse, R. In vivo depletion of CD8+ T lymphocytes abrogates protective immunity to African swine fever virus. J. Gen. Virol. 2005, 86, 2445–2450. [Google Scholar] [CrossRef] [PubMed]
- Onisk, D.V.; Borca, M.V.; Kutish, G.; Kramer, E.; Irusta, P.; Rock, D.L. Passively transferred African swine fever virus antibodies protect swine against lethal infection. Virology 1994, 198, 350–354. [Google Scholar] [CrossRef] [PubMed]
- Escribano, J.M.; Galindo, I.; Alonso, C. Antibody-mediated neutralization of African swine fever virus: Myths and facts. Virus Res. 2013, 173, 101–109. [Google Scholar] [CrossRef] [PubMed]
- Gómez-Puertas, P.; Rodríguez, F.; Ortega, A.; Oviedo, J.M.; Alonso, C.; Escribano, J.M. Improvement of African swine fever virus neutralization assay using recombinant viruses expressing chromogenic marker genes. J. Virol. Methods 1995, 55, 271–279. [Google Scholar] [CrossRef]
- Fernandez, A.; Perez, J.; Martin de las Mulas, J.; Carrasco, L.; Dominguez, J.; Sierra, M.A. Localization of African swine fever viral antigen, swine IgM, IgG and C1q in lung and liver tissues of experimentally infected pigs. J. Comp. Pathol. 1992, 107, 81–90. [Google Scholar] [CrossRef]
- Neilan, J.G.; Zsak, L.; Lu, Z.; Burrage, T.G.; Kutish, G.F.; Rock, D.L. Neutralizing antibodies to African swine fever virus proteins p30, p54, and p72 are not sufficient for antibody-mediated protection. Virology 2004, 319, 337–342. [Google Scholar] [CrossRef] [Green Version]
- Zsak, L.; Onisk, D.V.; Afonso, C.L.; Rock, D.L. Virulent African swine fever virus isolates are neutralized by swine immune serum and by monoclonal antibodies recognizing a 72-kDa viral protein. Virology 1993, 196, 596–602. [Google Scholar] [CrossRef]
- Krug, P.W.; Holinka, L.G.; O’Donnell, V.; Reese, B.; Sanford, B.; Fernandez-Sainz, I.; Gladue, D.P.; Arzt, J.; Rodriguez, L.; Risatti, G.R.; et al. The progressive adaptation of a georgian isolate of African swine fever virus to vero cells leads to a gradual attenuation of virulence in swine corresponding to major modifications of the viral genome. J. Virol. 2015, 89, 2324–2332. [Google Scholar] [CrossRef] [Green Version]
- Carlson, J.; O’Donnell, V.; Alfano, M.; Velazquez Salinas, L.; Holinka, L.G.; Krug, P.W.; Gladue, D.P.; Higgs, S.; Borca, M.V. Association of the Host Immune Response with Protection Using a Live Attenuated African Swine Fever Virus Model. Viruses 2016, 8, 291. [Google Scholar] [CrossRef]
- Borca, M.V.; Ramirez-Medina, E.; Silva, E.; Vuono, E.; Rai, A.; Pruitt, S.; Espinoza, N.; Velazquez-Salinas, L.; Gay, C.G.; Gladue, D.P. ASFV-G-∆I177L as an Effective Oral Nasal Vaccine against the Eurasia Strain of Africa Swine Fever. Viruses 2021, 13, 765. [Google Scholar] [CrossRef]
- Viñuela, E. African swine fever virus. Curr. Top. Microbiol. Immunol. 1985, 116, 151–170. [Google Scholar] [CrossRef] [PubMed]
- Hess, W.R. African swine fever: A reassessment. Adv. Vet. Sci. Comp. Med. 1981, 25, 39–69. [Google Scholar] [PubMed]
- Goatley, L.C.; Nash, R.H.; Andrews, C.; Hargreaves, Z.; Tng, P.; Reis, A.L.; Graham, S.P.; Netherton, C.L. Cellular and Humoral Immune Responses after Immunisation with Low Virulent African Swine Fever Virus in the Large White Inbred Babraham Line and Outbred Domestic Pigs. Viruses 2022, 14, 1487. [Google Scholar] [CrossRef] [PubMed]
Vaccine Type, Dose, and Route of Administration * | Challenge at dpv † | Number of Protected/ Total at Challenge †† |
---|---|---|
ASFV-G-Δ9GL/ΔUK (IM) 102 HAD | 28 | 3/9 |
ASFV-G-Δ9GL/ΔUK (IM) 104 HAD | 28 | 13/15 |
ASFV-G-Δ9GL/ΔUK (IM) 106 HAD | 28 | 15/15 |
ASFV-G-Δ9GL/ΔUK (IM) 104 HAD | 7 | 1/5 |
ASFV-G-Δ9GL/ΔUK (IM) 104 HAD | 14 | 5/5 |
ASFV-G-Δ9GL/ΔUK (IM) 104 HAD | 21 | 4/5 |
ASFV-G-ΔI177L (IM) 102 HAD | 28 | 20/20 |
ASFV-G-ΔI177L (IM) 106 HAD | 28 | 5/5 |
ASFV-G-ΔI177L (O/N) 106 HAD | 28 | 5/5 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Silva, E.B.; Krug, P.W.; Ramirez-Medina, E.; Valladares, A.; Rai, A.; Espinoza, N.; Gladue, D.P.; Borca, M.V. The Presence of Virus Neutralizing Antibodies Is Highly Associated with Protection against Virulent Challenge in Domestic Pigs Immunized with ASFV live Attenuated Vaccine Candidates. Pathogens 2022, 11, 1311. https://doi.org/10.3390/pathogens11111311
Silva EB, Krug PW, Ramirez-Medina E, Valladares A, Rai A, Espinoza N, Gladue DP, Borca MV. The Presence of Virus Neutralizing Antibodies Is Highly Associated with Protection against Virulent Challenge in Domestic Pigs Immunized with ASFV live Attenuated Vaccine Candidates. Pathogens. 2022; 11(11):1311. https://doi.org/10.3390/pathogens11111311
Chicago/Turabian StyleSilva, Ediane B., Peter W. Krug, Elizabeth Ramirez-Medina, Alyssa Valladares, Ayushi Rai, Nallely Espinoza, Douglas P. Gladue, and Manuel V. Borca. 2022. "The Presence of Virus Neutralizing Antibodies Is Highly Associated with Protection against Virulent Challenge in Domestic Pigs Immunized with ASFV live Attenuated Vaccine Candidates" Pathogens 11, no. 11: 1311. https://doi.org/10.3390/pathogens11111311