title: 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.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Raabe
authors.forename: C J
authors.initials: CJ
authors.lastname: Issel
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D004859:Equine Infectious Anemia / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006736:Horses; D007106:Immune Sera / Q000276:immunology; D007136:Immunoglobulins / Q000276:immunology; D004860:Infectious Anemia Virus, Equine / Q000276:immunology / Q000502:physiology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007106:Immune Sera; D007136:Immunoglobulins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D003165:Complement System Proteins