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

Abstract

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 replication and disease, depending on the immunization strategy used. This range of vaccine efficacy observed in vivo offers a unique opportunity for evaluating potential in vitro immune correlates of protection and enhancement. We describe here a comprehensive analysis and comparison of EIAV envelope-specific antibody responses elicited by attenuated, inactivated whole virus and envelope subunit vaccines to EIAV, and we evaluate the potential of in vitro antibody assays as correlates of protection or enhancement. Thus vaccine-induced serum antibody responses in experimentally immunized ponies at the day of challenge were assayed using a panel of quantitative, qualitative, and functional in vitro assays, including end- point titer of total and isotypic IgG, serum antibody avidity, conformational dependence, and serum neutralization. The results of these studies revealed substantial differences in the EIAV envelope-specific antibody responses elicited by the different vaccines, indicating the importance of envelope glycoprotein antigen presentation in determining the specificity of vaccine immunity. Although no single in vitro parameter provided a statistically significant correlate of protection or enhancement, the use of multiple parameters (titer, avidity index, and conformation ratio) could be used as a reliable correlate of vaccine protection and that the level of vaccine protection was closely associated with the development of mature antibody responses. These studies demonstrate the importance of using multiple antibody assays to evaluate lentiviral vaccine responses and emphasize the need for the development of new in vitro antibody assays that may provide more insight into vaccine protection and enhancement.