Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement.
Abstract: We have previously reported that immunization of ponies with a baculovirus-expressed recombinant surface unit envelope protein (rgp90) for equine infectious anemia virus (EIAV) resulted in enhancement of disease symptoms and virus replication in 4 of 4 vaccine recipients subjected to a heterologous virus challenge (rpg90 I vaccine trial) (Wang et al., 1994). To extend these studies of EIAV vaccine enhancement, two additional and independent rgp90 vaccine trials (rgp90 II and rgp90 III) were performed. Combined, a total of 13 ponies were immunized with the rgp90 immunogen using our standard vaccination procedures and challenged with a heterologous strain of EIAV. In contrast to the uniform enhancement observed in the rgp90 I vaccine trial, the severity of clinical symptoms varied markedly among the rgp90 recipients: 5 ponies experienced enhanced disease symptoms, 5 ponies experienced moderate disease symptoms, and 3 ponies remained asymptomatic. Of particular interest, in the 5 ponies with enhanced clinical symptoms was a severe thrombocytopenia (< or = 105,000 platelets/microliter) evident coincident with the first febrile episode following virus challenge. Thrombocytopenia was either absent (7/10 ponies) or substantially delayed (3/10 ponies) in naive control ponies inoculated with the standard EIAVPV challenge. Measurements of virus replication in the challenged vaccine recipients indicated a correlation between the level of viral RNA in plasma and the severity of the disease. Interestingly, an association was not observed between serum antibody reactivity to the vaccine or native viral antigens and the frequency of enhancement. Thus, these observations demonstrate a previously unrecognized complexity of rgp90 vaccine efficacy that has important implications for AIDS vaccine development.
Publication Date: 1998-06-06 PubMed ID: 9614876DOI: 10.1006/viro.1998.9142Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research presents a study on vaccine development for Equine Infectious Anemia Virus (EIAV), focusing on the effects of immunizing ponies with a recombinant surface unit envelope protein (rgp90). However, the intensity of disease symptoms varied among the vaccinated subjects.
Overview of the Research
The study is centered around the immunization of ponies using a recombinant envelope protein (rgp90) for the EIAV. Multiple vaccine trials were conducted, involving a total of 13 ponies following a standard vaccination procedure. The ponies were then challenged with a different strain of EIAV to evaluate the effectiveness of the vaccine.
Findings and Observations
- In the first trial (rgp90 I), all vaccinated ponies showed an enhancement of disease symptoms and virus replication.
- In the subsequent trials (rgp90 II and III), immunization with rgp90 led to a varying severity of clinical symptoms among the ponies: enhanced disease symptoms in 5, moderate symptoms in 5, and no symptoms in 3.
- Among those with enhanced symptoms, severe thrombocytopenia (a condition characterized by a deficiency of platelets in the blood) was observed. This condition coincided with the first fever episode following the virus challenge.
- Thrombocytopenia was absent or significantly delayed in the control group, which consisted of ponies inoculated with the standard EIAV challenge.
- A correlation was found between virus replication levels and the severity of the disease. However, no clear association was found between the immune response to the vaccine or native viral antigens and the frequency of disease enhancement.
Implications of the Research
The study reveals a previously unknown complexity in the efficacy of the rgp90 vaccine. Despite some ponies showing enhanced disease symptoms post-vaccination, others displayed moderate to no symptoms. The findings also suggest that virus replication levels might play a role in the severity of the disease. This could potentially influence aids in vaccine development. The research thus emphasizes the need for further studies to develop more effective vaccination strategies.
Cite This Article
APA
Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC.
(1998).
Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement.
Virology, 245(1), 151-162.
https://doi.org/10.1006/viro.1998.9142 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
MeSH Terms
- Animals
- Antibodies, Viral / immunology
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / prevention & control
- Glycoproteins / genetics
- Glycoproteins / immunology
- Immunization
- Infectious Anemia Virus, Equine / physiology
- Recombinant Proteins / genetics
- Recombinant Proteins / immunology
- Vaccines, Synthetic / immunology
- Viral Envelope Proteins / genetics
- Viral Envelope Proteins / immunology
- Viral Vaccines / immunology
- Virus Replication / immunology
Grant Funding
- 2R01 CA49296 / NCI NIH HHS
- 5R01 AI25850 / NIAID NIH HHS
- 5T32 AIO7487 / NIAID NIH HHS
Citations
This article has been cited 20 times.- 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.
- Patel JR, Heldens JG, Bakonyi T, Rusvai M. Important mammalian veterinary viral immunodiseases and their control.. Vaccine 2012 Feb 27;30(10):1767-81.
- 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.
- Prieto C, Martínez-Lobo FJ, Díez-Fuertes F, Aguilar-Calvo P, Simarro I, Castro JM. Immunisation of pigs with a major envelope protein sub-unit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) results in enhanced clinical disease following experimental challenge.. Vet J 2011 Sep;189(3):323-9.
- 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.
- 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.
- Chung C, Mealey RH, McGuire TC. Evaluation of high functional avidity CTL to Gag epitope clusters in EIAV carrier horses.. Virology 2005 Nov 25;342(2):228-39.
- 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.
- Chung C, Mealey RH, McGuire TC. CTL from EIAV carrier horses with diverse MHC class I alleles recognize epitope clusters in Gag matrix and capsid proteins.. Virology 2004 Sep 15;327(1):144-54.
- 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.
- Harrold SM, Cook SJ, Cook RF, Rushlow KE, Issel CJ, Montelaro RC. Tissue sites of persistent infection and active replication of equine infectious anemia virus during acute disease and asymptomatic infection in experimentally infected equids.. J Virol 2000 Apr;74(7):3112-21.
- Li F, Leroux C, Craigo JK, Cook SJ, Issel CJ, Montelaro RC. The S2 gene of equine infectious anemia virus is a highly conserved determinant of viral replication and virulence properties in experimentally infected ponies.. J Virol 2000 Jan;74(1):573-9.
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