Sa. Hammond et al., Evaluation of antibody parameters as potential correlates of protection orenhancement by experimental vaccines to equine infectious anemia virus, VIROLOGY, 262(2), 1999, pp. 416-430
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.