Evaluation of antibody parameters as potential correlates of protection orenhancement by experimental vaccines to equine infectious anemia virus

We previously demonstrated in trials of a variety of experimental Vaccines to equine infectious anemia virus (EIAV) a remarkable spectrum of efficacy ranging from sterilizing protection to severe enhancement of virus replicat ion and disease, depending on the immunization strategy used. This range of vaccine efficacy observed in vivo offers a unique opportunity for evaluati ng potential in vitro immune correlates of protection and enhancement We de scribe here a comprehensive analysis and comparison of EIAV envelope-specif ic antibody responses elicited by attenuated, inactivated whole virus and e nvelope subunit vaccines to EIAV, end we evaluate the potential of in vitro antibody assays as correlates of protection or enhancement Thus vaccine-in duced serum antibody responses in experimentally immunized ponies at the da y of challenge were assayed using a panel of quantitative, qualitative, and functional in vitro assays, including end-point titer of total and isotypi c IgG, serum antibody avidity, conformational dependence, and serum neutral ization. The results of these studies revealed substantial differences in t he EIAV envelope-specific antibody responses elicited by the different vacc ines, indicating the importance of envelope glycoprotein antigen presentati on in determining the specificity of Vaccine immunity. Although no single i n vitro parameter provided a statistically significant correlate of protect ion or enhancement, the use of multiple parameters (titer, avidity index, a nd conformation ratio) could be used as a reliable correlate of vaccine pro tection and that the level of Vaccine protection was closely associated wit h the development of mature antibody responses. These studies demonstrate t he importance of using multiple antibody assays to evaluate lentiviral vacc ine responses and emphasize the need for the development of new in vitro an tibody assays that may provide more insight into vaccine protection and enh ancement. (C) 1999 Academic Press.