In vitro antibody-dependent enhancement assays are insensitive indicators of in vivo vaccine enhancement of equine infectious anemia virus.
Abstract: We have previously demonstrated a high propensity for enhancement of virus replication and disease resulting from experimental immunization of ponies with a baculovirus recombinant envelope (rgp90) vaccine from equine infectious anemia virus (EIAV). The current studies were undertaken to examine the correlation between the observed in vivo vaccine enhancement and in vitro assays for antibody-dependent enhancement (ADE) of EIAV replication. Toward this goal an optimized EIAV in vitro enhancement assay was developed using primary equine macrophage cells and used to evaluate the enhancement properties of immune serum taken from rgp90 immunized ponies that displayed various levels of vaccine enhancement after experimental challenge with EIAV. For comparison, we analyzed in parallel immune serum samples from a group of ponies immunized with a viral envelope subunit vaccine (LL-gp) that produced sterile protection from EIAV challenge. The results of these assays demonstrated that the rgp90 immune serum had a greater propensity for in vitro enhancement of EIAV replication than serum from the protected LL-gp immunized ponies; in vitro enhancement levels for the rgp90 immune sera averaged about 1.5, with a maximum enhancement value of about 2.0. While distinguishing between immune serum produced by the rgp90 and LL-gp immunizations, the in vitro enhancement assay failed to reliably correlate with the severity of in vivo enhancement observed among the rgp90 vaccine recipients. Vaccinated ponies that experienced moderate to no disease signs displayed levels of in vitro enhancement similar to those of ponies that experienced severe and fatal enhancement of disease after viral challenge. The observed in vitro enhancement was demonstrated to be dependent on serum immunoglobulin, but independent of complement. These studies demonstrate in the EIAV system that in vitro ADE assays appear to be relatively insensitive indicators of the severity of in vivo enhancement and that relatively low levels of in vitro ADE can be associated with severe to fatal enhancement of virus replication and disease in vivo. These observations suggest that relatively low levels of serum ADE observed in other lentivirus systems, including HIV-1, may have more profound effects on in vivo virus replication and disease than previously recognized.
Copyright 1999 Academic Press.
Publication Date: 1999-07-02 PubMed ID: 10388665DOI: 10.1006/viro.1999.9772Google 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 conducted aimed to analyze the link between in vivo vaccine enhancement and in vitro assays for antibody-dependent enhancement (ADE) in the replication of equine infectious anemia virus (EIAV). The results demonstrated that the in vitro assays are relatively poor indicators of the in vivo enhancement.
Research Objective and Methodology
- The research aimed to investigate if there is a correlation between in vivo vaccine enhancement and in vitro assays for ADE of EIAV replication. The team built an optimized EIAV in vitro enhancement assay using primary equine macrophage cells.
- To compare the efficacy of different vaccines, immune serum taken from ponies immunized with rgp90 and a viral envelope subunit vaccine LL-gp were analyzed. The rgp90 immunized ponies displayed varying levels of vaccine enhancement.
Research Findings
- The research found that rgp90 immune serum had a higher propensity for in vitro enhancement of EIAV replication compared to serum from ponies protected by LL-gp immunization.
- Despite this distinction, the in vitro enhancement assay did not consistently correlate with the severity of in vivo enhancement among the rgp90 vaccinated ponies. Some vaccinated ponies with negative to moderate disease symptoms demonstrated levels of in vitro enhancement matching those of ponies with severe, fatal enhancement of the disease after viral challenge.
- Furthermore, the observed in vitro enhancement was discovered to be dependent on serum immunoglobulin but was not influenced by complement.
Conclusions and Implications
- From the research outcomes, it was concluded that in vitro ADE assays are not very sensitive indicators of the severity of in vivo enhancement.
- It was noted that relatively low levels of in vitro ADE can be linked to severe or fatal enhancement of virus replication and disease in vivo. This suggests that low levels of serum ADE observed in other lentivirus systems, such as HIV-1, could have a more profound effect on in vivo virus replication and disease than previously understood.
Cite This Article
APA
Raabe ML, Issel CJ, Montelaro RC.
(1999).
In vitro antibody-dependent enhancement assays are insensitive indicators of in vivo vaccine enhancement of equine infectious anemia virus.
Virology, 259(2), 416-427.
https://doi.org/10.1006/viro.1999.9772 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
MeSH Terms
- Animals
- Antibodies, Viral / immunology
- Antibody-Dependent Enhancement / immunology
- Complement System Proteins / immunology
- Equine Infectious Anemia / immunology
- Equine Infectious Anemia / prevention & control
- Equine Infectious Anemia / virology
- Horses
- Immune Sera / immunology
- Immunoglobulins / immunology
- Infectious Anemia Virus, Equine / immunology
- Infectious Anemia Virus, Equine / physiology
- Vaccines, Synthetic / immunology
- Viral Envelope Proteins / administration & dosage
- Viral Envelope Proteins / immunology
- Viral Vaccines / administration & dosage
- Viral Vaccines / immunology
- Virus Replication / immunology
Grant Funding
- 5RO1 AI25850 / NIAID NIH HHS
- 5T32 AIO7487 / NIAID NIH HHS
Citations
This article has been cited 11 times.- Khandia R, Munjal A, Dhama K, Karthik K, Tiwari R, Malik YS, Singh RK, Chaicumpa W. Modulation of Dengue/Zika Virus Pathogenicity by Antibody-Dependent Enhancement and Strategies to Protect Against Enhancement in Zika Virus Infection.. Front Immunol 2018;9:597.
- 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).
- 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.
- 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.
- 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.
- 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.
- Staprans SI, Barry AP, Silvestri G, Safrit JT, Kozyr N, Sumpter B, Nguyen H, McClure H, Montefiori D, Cohen JI, Feinberg MB. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein.. Proc Natl Acad Sci U S A 2004 Aug 31;101(35):13026-31.
- Takada A, Feldmann H, Ksiazek TG, Kawaoka Y. Antibody-dependent enhancement of Ebola virus infection.. J Virol 2003 Jul;77(13):7539-44.
- Subbramanian RA, Xu J, Toma E, Morisset R, Cohen EA, Menezes J, Ahmad A. Comparison of human immunodeficiency virus (HIV)-specific infection-enhancing and -inhibiting antibodies in AIDS patients.. J Clin Microbiol 2002 Jun;40(6):2141-6.
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