FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Virology1994; 199(1); 247-251; doi: 10.1006/viro.1994.1120

Enhancement of EIAV replication and disease by immunization with a baculovirus-expressed recombinant envelope surface glycoprotein.

Abstract: The potential for antibody-dependent enhancement of replication of macrophage/monocyte tropic viruses has posed a significant problem in the development of vaccines for several animal and human viruses and has raised significant concern in the design of potential AIDS vaccines. Using the previously described equine infectious anemia virus/Shetland pony system as a model for HIV-1 vaccine development, we have evaluated the efficacy of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. The results of these trials demonstrate not only that the recombinant vaccine failed to protect against infection by standard homologous and heterologous EIAV challenge strains, but that it resulted in a marked enhancement of virus replication and exacerbation of disease in immunized ponies exposed to the heterologous virus strain. Thus, the recombinant EIAV gp90 vaccine provides a novel in vivo model for examining in detail the mechanisms of immune enhancement of a lentivirus infection and for evaluating strategies to avoid the production of deleterious immune responses in AIDS vaccine design.
Get Full Text
Publication Date: 1994-02-15 PubMed ID: 8116252DOI: 10.1006/viro.1994.1120Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates how immunization with a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein affects replication and severity of equine infectious anemia virus (EIAV). Findings reveal that instead of shielding against EIAV, the vaccine escalated virus replication and worsened the disease in immunized ponies exposed to a different virus strain.

Introduction

In this research, scientists made use of the equine infectious anemia virus/Shetland pony system to model HIV-1 vaccine development. The study’s primary goal was to assess the effectiveness of a recombinant subunit vaccine containing a baculovirus-expressed envelope surface glycoprotein (gp90) of EIAV. This experiment is critical to understanding the risks posed by the potentially damaging effects of vaccines in battling macrophage/monocyte tropic viruses like EIAV and HIV-1.

Results

Findings from the study were surprising and counter-intuitive. Specifically, the results showed:

  • The recombinant vaccine did not successfully protect the subjects against infection by standard homologous and heterologous EIAV challenge strains. This lack of vaccine-induced immunity was a critical failure in the experiment.
  • Rather than offering protection, the recombinant vaccine escalated virus replication, intensifying the disease’s severity in the immunized ponies when they were exposed to a different strain of the virus. This is indicative of an immune enhancement of an infection, which is a risk factor for vaccine development,

Conclusion and Implications

The conclusions of the research suggest serious implications for vaccine development—particularly for macrophage/monocyte tropic viruses. One potential outcome from this study is that current approaches to developing vaccines, especially those targeted against HIV-1, might result in enhancing an infection rather than preventing one.

The recombinant EIAV gp90 vaccine provides researchers with a potent tool—an in vivo model—for further illuminating the mechanisms of immune enhancement of a lentivirus infection. Using this platform, scientists can evaluate strategies to avoid creating harmful immune responses in the design of AIDS vaccines.

This research underscores the necessity of thorough experimentation and careful interpretation of results in the development of vaccines. The study also raises crucial questions regarding the negative implications of certain immunization strategies, which could lead to increased disease severity instead of protection.

Cite This Article

APA
Wang SZ, Rushlow KE, Issel CJ, Cook RF, Cook SJ, Raabe ML, Chong YH, Costa L, Montelaro RC. (1994). Enhancement of EIAV replication and disease by immunization with a baculovirus-expressed recombinant envelope surface glycoprotein. Virology, 199(1), 247-251. https://doi.org/10.1006/viro.1994.1120

Publication

Virology
ISSN: 0042-6822
NlmUniqueID: 0110674
Country: United States
Language: English
Volume: 199
Issue: 1
Pages: 247-251

Researcher Affiliations

Wang, S Z
  • Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Rushlow, K E
    Issel, C J
      Cook, R F
        Cook, S J
          Raabe, M L
            Chong, Y H
              Costa, L
                Montelaro, R C

                  MeSH Terms

                  • AIDS Vaccines / pharmacology
                  • Animals
                  • Baculoviridae
                  • Cloning, Molecular
                  • Equine Infectious Anemia / immunology
                  • Equine Infectious Anemia / microbiology
                  • Equine Infectious Anemia / prevention & control
                  • Horses
                  • Humans
                  • Infectious Anemia Virus, Equine / genetics
                  • Infectious Anemia Virus, Equine / immunology
                  • Infectious Anemia Virus, Equine / physiology
                  • Membrane Glycoproteins / genetics
                  • Membrane Glycoproteins / immunology
                  • Recombinant Proteins / immunology
                  • Vaccines, Synthetic / pharmacology
                  • Viral Envelope Proteins / genetics
                  • Viral Envelope Proteins / immunology
                  • Viral Vaccines / pharmacology
                  • Virus Replication

                  Grant Funding

                  • R01AI25850 / NIAID NIH HHS

                  Citations

                  This article has been cited 28 times.
                  1. Andrade LAF, Versiani AF, Barbosa-Stancioli EF, Dos Reis JKP, Dos Reis JGAC, da Fonseca FG. Developing a Feline Immunodeficiency Virus Subtype B Vaccine Prototype Using a Recombinant MVA Vector. Vaccines (Basel) 2022 Oct 14;10(10).
                    doi: 10.3390/vaccines10101717pubmed: 36298582google scholar: lookup
                  2. 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).
                    doi: 10.3390/vetsci4010007pubmed: 29056666google scholar: lookup
                  3. 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.
                    doi: 10.3390/v5122963pubmed: 24316675google scholar: lookup
                  4. 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.
                    doi: 10.1371/journal.pone.0066093pubmed: 23785473google scholar: lookup
                  5. 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.
                    doi: 10.1186/1742-4690-8-16pubmed: 21401915google scholar: lookup
                  6. 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.
                    doi: 10.1016/j.vaccine.2010.10.003pubmed: 20955830google scholar: lookup
                  7. 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.
                    doi: 10.1016/j.tvjl.2010.07.010pubmed: 20713312google scholar: lookup
                  8. 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.
                    doi: 10.1016/j.vaccine.2009.02.048pubmed: 19368787google scholar: lookup
                  9. Huisman W, Martina BE, Rimmelzwaan GF, Gruters RA, Osterhaus AD. Vaccine-induced enhancement of viral infections. Vaccine 2009 Jan 22;27(4):505-12.
                    doi: 10.1016/j.vaccine.2008.10.087pubmed: 19022319google scholar: lookup
                  10. 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.
                    doi: 10.1371/journal.ppat.0030169pubmed: 17983270google scholar: lookup
                  11. 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.
                    doi: 10.1016/j.vaccine.2006.09.040pubmed: 17023099google scholar: lookup
                  12. Pistello M, Bonci F, Flynn JN, Mazzetti P, Isola P, Zabogli E, Camerini V, Matteucci D, Freer G, Pelosi P, Bendinelli M. AIDS vaccination studies with an ex vivo feline immunodeficiency virus model: analysis of the accessory ORF-A protein and DNA as protective immunogens. J Virol 2006 Sep;80(18):8856-68.
                    doi: 10.1128/JVI.00397-06pubmed: 16940498google scholar: lookup
                  13. 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.
                    doi: 10.1016/j.virol.2005.07.033pubmed: 16139857google scholar: lookup
                  14. 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.
                    doi: 10.1128/CDLI.11.6.1120-1129.2004pubmed: 15539516google scholar: lookup
                  15. Cancel-Tirado SM, Evans RB, Yoon KJ. Monoclonal antibody analysis of porcine reproductive and respiratory syndrome virus epitopes associated with antibody-dependent enhancement and neutralization of virus infection. Vet Immunol Immunopathol 2004 Dec 8;102(3):249-62.
                    doi: 10.1016/j.vetimm.2004.09.017pubmed: 15507309google scholar: lookup
                  16. 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.
                    doi: 10.1016/j.virol.2004.06.035pubmed: 15327905google scholar: lookup
                  17. Gould SJ, Booth AM, Hildreth JE. The Trojan exosome hypothesis. Proc Natl Acad Sci U S A 2003 Sep 16;100(19):10592-7.
                    doi: 10.1073/pnas.1831413100pubmed: 12947040google scholar: lookup
                  18. Leroux C, Craigo JK, Issel CJ, Montelaro RC. Equine infectious anemia virus genomic evolution in progressor and nonprogressor ponies. J Virol 2001 May;75(10):4570-83.
                    doi: 10.1128/JVI.75.10.4570-4583.2001pubmed: 11312327google scholar: lookup
                  19. Valas S, Benoit C, Baudry C, Perrin G, Mamoun RZ. Variability and immunogenicity of caprine arthritis-encephalitis virus surface glycoprotein. J Virol 2000 Jul;74(13):6178-85.
                    doi: 10.1128/jvi.74.13.6178-6185.2000pubmed: 10846103google scholar: lookup
                  20. 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.
                    doi: 10.1128/jvi.74.13.5968-5981.2000pubmed: 10846078google scholar: lookup
                  21. Lonning SM, Zhang W, McGuire TC. Gag protein epitopes recognized by CD4(+) T-helper lymphocytes from equine infectious anemia virus-infected carrier horses. J Virol 1999 May;73(5):4257-65.
                    doi: 10.1128/JVI.73.5.4257-4265.1999pubmed: 10196322google scholar: lookup
                  22. Connor RI, Korber BT, Graham BS, Hahn BH, Ho DD, Walker BD, Neumann AU, Vermund SH, Mestecky J, Jackson S, Fenamore E, Cao Y, Gao F, Kalams S, Kunstman KJ, McDonald D, McWilliams N, Trkola A, Moore JP, Wolinsky SM. Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J Virol 1998 Feb;72(2):1552-76.
                    doi: 10.1128/JVI.72.2.1552-1576.1998pubmed: 9445059google scholar: lookup
                  23. Cook RF, Leroux C, Cook SJ, Berger SL, Lichtenstein DL, Ghabrial NN, Montelaro RC, Issel CJ. Development and characterization of an in vivo pathogenic molecular clone of equine infectious anemia virus. J Virol 1998 Feb;72(2):1383-93.
                    doi: 10.1128/JVI.72.2.1383-1393.1998pubmed: 9445039google scholar: lookup
                  24. Richardson J, Moraillon A, Baud S, Cuisinier AM, Sonigo P, Pancino G. Enhancement of feline immunodeficiency virus (FIV) infection after DNA vaccination with the FIV envelope. J Virol 1997 Dec;71(12):9640-9.
                    doi: 10.1128/JVI.71.12.9640-9649.1997pubmed: 9371628google scholar: lookup
                  25. Montefiori DC. Role of complement and Fc receptors in the pathogenesis of HIV-1 infection. Springer Semin Immunopathol 1997;18(3):371-90.
                    doi: 10.1007/BF00813504pubmed: 9089955google scholar: lookup
                  26. Lombardi S, Garzelli C, Pistello M, Massi C, Matteucci D, Baldinotti F, Cammarota G, da Prato L, Bandecchi P, Tozzini F. A neutralizing antibody-inducing peptide of the V3 domain of feline immunodeficiency virus envelope glycoprotein does not induce protective immunity. J Virol 1994 Dec;68(12):8374-9.
                    doi: 10.1128/JVI.68.12.8374-8379.1994pubmed: 7966629google scholar: lookup
                  27. Bertoni G, Zahno ML, Zanoni R, Vogt HR, Peterhans E, Ruff G, Cheevers WP, Sonigo P, Pancino G. Antibody reactivity to the immunodominant epitopes of the caprine arthritis-encephalitis virus gp38 transmembrane protein associates with the development of arthritis. J Virol 1994 Nov;68(11):7139-47.
                    doi: 10.1128/JVI.68.11.7139-7147.1994pubmed: 7933096google scholar: lookup
                  28. Cook RF, Berger SL, Rushlow KE, McManus JM, Cook SJ, Harrold S, Raabe ML, Montelaro RC, Issel CJ. Enhanced sensitivity to neutralizing antibodies in a variant of equine infectious anemia virus is linked to amino acid substitutions in the surface unit envelope glycoprotein. J Virol 1995 Mar;69(3):1493-9.
                    doi: 10.1128/JVI.69.3.1493-1499.1995pubmed: 7853482google scholar: lookup
                  Subscribe to our newsletter
                  Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.