Evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus.
Abstract: We previously demonstrated in trials of a variety of experimental vaccines to equine infectious anemia virus (EIAV) a remarkable spectrum of efficacy ranging from sterilizing protection to severe enhancement of virus replication and disease, depending on the immunization strategy used. This range of vaccine efficacy observed in vivo offers a unique opportunity for evaluating potential in vitro immune correlates of protection and enhancement. We describe here a comprehensive analysis and comparison of EIAV envelope-specific antibody responses elicited by attenuated, inactivated whole virus and envelope subunit vaccines to EIAV, and we evaluate the potential of in vitro antibody assays as correlates of protection or enhancement. Thus vaccine-induced serum antibody responses in experimentally immunized ponies at the day of challenge were assayed using a panel of quantitative, qualitative, and functional in vitro assays, including end-point titer of total and isotypic IgG, serum antibody avidity, conformational dependence, and serum neutralization. The results of these studies revealed substantial differences in the EIAV envelope-specific antibody responses elicited by the different vaccines, indicating the importance of envelope glycoprotein antigen presentation in determining the specificity of vaccine immunity. Although no single in vitro parameter provided a statistically significant correlate of protection or enhancement, the use of multiple parameters (titer, avidity index, and conformation ratio) could be used as a reliable correlate of vaccine protection and that the level of vaccine protection was closely associated with the development of mature antibody responses. These studies demonstrate the importance of using multiple antibody assays to evaluate lentiviral vaccine responses and emphasize the need for the development of new in vitro antibody assays that may provide more insight into vaccine protection and enhancement.
Copyright 1999 Academic Press.
Publication Date: 1999-09-30 PubMed ID: 10502520DOI: 10.1006/viro.1999.9939Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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This research study undertakes a thorough analysis of the immune response elicited by different experimental vaccines to equine infectious anemia virus (EIAV), with a focus on EIAV envelope-specific antibody reactions. The study explores whether specific in vitro antibody tests can correlate with the level of vaccine protection or enhancement in treated ponies.
Study Overview
- The research is based on prior trials where a variety of experimental vaccines, designed to treat equine infectious anemia virus (EIAV), showed varied degrees of efficacy. Outcomes ranged from full protection against the virus to severe enhancement of virus replication and disease. The vaccines’ diverse effects provided a unique opportunity to evaluate potential immune responses.
- Using a comprehensive analysis and comparison technique, researchers examined the EIAV envelope-specific antibody responses elicited by various types of vaccines. These included attenuated vaccines, inactivated whole virus vaccines, and envelope subunit vaccines.
- The study aimed to determine whether in vitro antibody tests could serve as indicators of protection or enhancement offered by each vaccine.
Methodology and Findings
- Vaccine-induced serum antibody responses in immunized ponies were assessed on the challenge day. This assessment included a host of quantitative, qualitative, and functional in vitro assays, such as the end-point titer of total and isotypic IgG, serum antibody avidity, conformational dependence, and serum neutralization.
- The study identified substantial differences in EIAV envelope-specific antibody responses elicited by the different vaccines. This highlighted the importance of the envelope glycoprotein antigen presentation in defining the specificity of vaccine-triggered immunity.
- No single in vitro parameter significantly correlated with protection or enhancement. However, using a combination of multiple parameters (titer, avidity index, and conformation ratio) could reliably indicate vaccine protection. Furthermore, the level of vaccine protection was closely associated with the development of mature antibody responses.
Conclusions and Implications
- The research underscores the importance of using multiple antibody assays to evaluate lentiviral vaccine responses.
- It emphasizes the need to develop new in vitro antibody assays that may provide more insight into vaccine protection and enhancement.
- Through their findings, the researchers underlined the potential of using antibody parameters as correlates of protection or enhancement in experimental EIAV vaccines.
Cite This Article
APA
Hammond SA, Raabe ML, Issel CJ, Montelaro RC.
(1999).
Evaluation of antibody parameters as potential correlates of protection or enhancement by experimental vaccines to equine infectious anemia virus.
Virology, 262(2), 416-430.
https://doi.org/10.1006/viro.1999.9939 Publication
Researcher Affiliations
- School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA.
MeSH Terms
- Animals
- Antibodies, Viral / biosynthesis
- Antibodies, Viral / immunology
- Antibody Affinity / immunology
- Epitopes / immunology
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / prevention & control
- Equine Infectious Anemia / virology
- Horses
- Immunoglobulin G / biosynthesis
- Immunoglobulin G / immunology
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / growth & development
- Infectious Anemia Virus, Equine / immunology
- Neutralization Tests
- Protein Conformation
- Time Factors
- Vaccination
- Vaccines, Attenuated / immunology
- Vaccines, Inactivated / immunology
- Vaccines, Synthetic / immunology
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
- Viral Vaccines / genetics
- Viral Vaccines / immunology
Grant Funding
- 5RO1-AI25850 / NIAID NIH HHS
- 5T32-AI07487 / NIAID NIH HHS
Citations
This article has been cited 18 times.- Hosie MJ, Techakriengkrai N, Bęczkowski PM, Harris M, Logan N, Willett BJ. The Comparative Value of Feline Virology Research: Can Findings from the Feline Lentiviral Vaccine Be Translated to Humans?. Vet Sci 2017 Jan 28;4(1).
- Liu C, Cook SJ, Craigo JK, Cook FR, Issel CJ, Montelaro RC, Horohov DW. Epitope shifting of gp90-specific cellular immune responses in EIAV-infected ponies.. Vet Immunol Immunopathol 2014 Oct 15;161(3-4):161-9.
- Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X. Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain.. Vet Res 2014 Aug 9;45(1):82.
- Sholukh AM, Byrareddy SN, Shanmuganathan V, Hemashettar G, Lakhashe SK, Rasmussen RA, Watkins JD, Vyas HK, Thorat S, Brandstoetter T, Mukhtar MM, Yoon JK, Novembre FJ, Villinger F, Landucci G, Forthal DN, Ratcliffe S, Tuero I, Robert-Guroff M, Polonis VR, Bilska M, Montefiori DC, Johnson WE, Ertl HC, Ruprecht RM. Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.. Retrovirology 2014 Jan 20;11:8.
- Vargas-Inchaustegui DA, Robert-Guroff M. Fc receptor-mediated immune responses: new tools but increased complexity in HIV prevention.. Curr HIV Res 2013 Jul;11(5):407-20.
- Craigo JK, Ezzelarab C, Montelaro RC. Development of a high throughput, semi-automated, infectious center cell-based ELISA for equine infectious anemia virus.. J Virol Methods 2012 Nov;185(2):221-7.
- Willey S, Aasa-Chapman MM, O'Farrell S, Pellegrino P, Williams I, Weiss RA, Neil SJ. Extensive complement-dependent enhancement of HIV-1 by autologous non-neutralising antibodies at early stages of infection.. Retrovirology 2011 Mar 14;8:16.
- Craigo JK, Barnes S, Cook SJ, Issel CJ, Montelaro RC. Divergence, not diversity of an attenuated equine lentivirus vaccine strain correlates with protection from disease.. Vaccine 2010 Nov 29;28(51):8095-104.
- Liu L, Wan Y, Wu L, Sun J, Li H, Li H, Ma L, Shao Y. Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine.. Retrovirology 2010 Sep 1;7:71.
- Craigo JK, Barnes S, Zhang B, Cook SJ, Howe L, Issel CJ, Montelaro RC. An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family.. Retrovirology 2009 Oct 20;6:95.
- Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen.. Vaccine 2009 Apr 21;27(18):2453-68.
- Huisman W, Martina BE, Rimmelzwaan GF, Gruters RA, Osterhaus AD. Vaccine-induced enhancement of viral infections.. Vaccine 2009 Jan 22;27(4):505-12.
- Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition.. J Virol 2008 Apr;82(8):4052-63.
- Shan M, Klasse PJ, Banerjee K, Dey AK, Iyer SP, Dionisio R, Charles D, Campbell-Gardener L, Olson WC, Sanders RW, Moore JP. HIV-1 gp120 mannoses induce immunosuppressive responses from dendritic cells.. PLoS Pathog 2007 Nov;3(11):e169.
- Craigo JK, Durkin S, Sturgeon TJ, Tagmyer T, Cook SJ, Issel CJ, Montelaro RC. Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.. Vaccine 2007 Jan 15;25(5):834-45.
- Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.. J Virol 2005 Mar;79(5):2666-77.
- Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, Montelaro RC. A live attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses.. J Virol 2003 Jul;77(13):7244-53.
- Hammond SA, Li F, McKeon BM Sr, Cook SJ, Issel CJ, Montelaro RC. Immune responses and viral replication in long-term inapparent carrier ponies inoculated with equine infectious anemia virus.. J Virol 2000 Jul;74(13):5968-81.
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