A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus.
Abstract: Immunization regimens that induce a broadly reactive cytolytic T lymphocyte (CTL) response specific for lentiviral antigens have emerged as the leading candidates in efficacy trials conducted in both animal modelshumans. To date, lentivirus vaccination strategies have overlooked one such immunization strategy, namely the use of particulate antigens. To evaluate the efficacy of targeting antigen into the phagocytic pathway to elicit a cell-mediated immune response to lentiviral antigens, we initiated the first study of a particulate-based vaccination protocol using a large animal model system. Gradient-purified equine infectious anemia virus (EIAV) was covalently coupled to glutaraldehyde-activated iron oxide beads. In vitro studies demonstrated the effectiveness of the inactivated whole virus particulate to prime antigen presenting cells for the activationexpansion of virus-specific CD8(+) CTL. The in vivo effectiveness of the particulate antigen was evaluated by experimental immunization of ponies. Ponies receiving the viral particulate vaccinechallenged with infectious EIAV had a delayed progression to diseasea reduced viral load compared with infected ponies that had not been vaccinated. Interestingly, in vitro virus-specific CTL activity was detected in only one of four immunized animals at the day of challenge. The beneficial effects of the particulate vaccine regimen were not clearly associated with any in vitro measurable parameters of the virus-specific cellular or humoral immune responses elicited by the vaccine at the day of challenge. However, within 3 weeks after virus challenge, anamnestic humoral responses characterized by a rapid emergence of neutralizing activity in the seruma predominance of conformationally dependent epitopes recognized by virus-specific antibodies were observed in the vaccinates. Taken together, further studies are clearly warranted in large animal model systems using a particulate-based vaccine regimen considering the beneficial effects of this regimen in our studythe protective effects of particulate antigen delivery in the murine model.
Copyright 1999 Academic Press.
Publication Date: 1999-02-03 PubMed ID: 9927572DOI: 10.1006/viro.1998.9550Google 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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The research discusses an experiment which aimed to evaluate the effectiveness of a particulate viral protein vaccine in reducing viral load and delaying disease progression in ponies infected with equine infectious anemia virus (EIAV). The results suggested that the vaccine showed promise in achieving these two key benchmarks, despite some measurable parameters at the day of challenge not clearly associating with the vaccine’s beneficial effects.
Immunization Strategy and Antigen Targeting
- The study involves the use of particulate antigens as part of the immunization strategy. Careful attention was given to directing the antigen to the phagocytic pathway in order to stimulate a cell-mediated immune response.
- Utilizing a large animal model system, gradient-purified EIAV was covalently coupled with glutaraldehyde-activated iron oxide beads.
- In vitro studies confirmed the effectiveness of the inactivated whole virus particulate in prepping antigen presenting cells for the activation and expansion of virus-specific CD8(+) CTL (cytolytic T lymphocyte), which play an integral role in combating viral infections.
Immunization and Disease Progression in Ponies
- Ponies were experimentally immunized with the viral particulate vaccine before being infected with infectious EIAV.
- Ponies receiving the vaccine showed a delay in disease progression and a reduction in viral load compared to infected ponies that had not been vaccinated.
- However, virus-specific CTL activity was only detectable in one out of four immunized animals at the day of challenge. Therefore, the reasons behind the vaccine’s beneficial effects weren’t clear when observing in vitro measurable parameters of the virus-specific cellular or humoral immune responses triggered by the vaccine at the day of challenge.
Conclusion and Further Studies
- Three weeks post virus challenge, vaccinated animals presented ‘anamnestic’ (secondary) humoral responses, including a rapid emergence of neutralizing activity in the serum and a prevalence of conformationally dependent epitopes recognized by virus-specific antibodies.
- In spite of uncertain in vitro associations, the study suggested the particulate-based vaccine regimen showed promise, warranting further studies in large animal model systems.
- The implications in treating EIAV and possibly other lentiviruses by means of particulate antigen delivery, as supported also by observations in the murine model, make this regimen worth exploring further.
Cite This Article
APA
Hammond SA, Cook SJ, Falo LD, Issel CJ, Montelaro RC.
(1999).
A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus.
Virology, 254(1), 37-49.
https://doi.org/10.1006/viro.1998.9550 Publication
Researcher Affiliations
- Departments of Molecular Genetics and Biochemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261, USA.
MeSH Terms
- Animals
- Disease Progression
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / prevention & control
- Ferric Compounds
- Horses
- Immunity, Cellular
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / physiology
- T-Lymphocytes / immunology
- Vaccination
- Viral Load
- Viral Proteins / immunology
- Viral Vaccines / immunology
- Virion / immunology
Grant Funding
- 5RO1-AI25850 / NIAID NIH HHS
- 5T32-AI07487 / NIAID NIH HHS
Citations
This article has been cited 14 times.- Du C, Ma J, Liu Q, Li YF, He XJ, Lin YZ, Wang XF, Meng QW, Wang X, Zhou JH. Mice transgenic for equine cyclin T1 and ELR1 are susceptible to equine infectious anemia virus infection. Retrovirology 2015 Apr 28;12:36.
- Craigo JK, Montelaro RC. Lessons in AIDS vaccine development learned from studies of equine infectious, anemia virus infection and immunity. Viruses 2013 Dec 2;5(12):2963-76.
- Craigo JK, Ezzelarab C, Cook SJ, Chong L, Horohov D, Issel CJ, Montelaro RC. Envelope determinants of equine lentiviral vaccine protection. PLoS One 2013;8(6):e66093.
- Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Yang K, Zhou J, Shen R, Zhang X, Shao Y. A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine. Viral Immunol 2012 Dec;25(6):477-84.
- 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.
- 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.
- 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.
- Fraser DG, Leib SR, Zhang BS, Mealey RH, Brown WC, McGuire TC. Lymphocyte proliferation responses induced to broadly reactive Th peptides did not protect against equine infectious anemia virus challenge. Clin Diagn Lab Immunol 2005 Aug;12(8):983-93.
- 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.
- Jin S, Issel CJ, Montelaro RC. Serological method using recombinant S2 protein to differentiate equine infectious anemia virus (EIAV)-infected and EIAV-vaccinated horses. Clin Diagn Lab Immunol 2004 Nov;11(6):1120-9.
- Fraser DG, Mealey RH, McGuire TC. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. Immunogenetics 2003 Oct;55(7):508-14.
- 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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