MATURATION OF THE CELLULAR AND HUMORAL IMMUNE-RESPONSES TO PERSISTENTINFECTION IN HORSES BY EQUINE INFECTIOUS-ANEMIA VIRUS IS A COMPLEX AND LENGTHY PROCESS

Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied , To date, no detailed study addressing in parallel both the humoral a nd cellular immune responses induced in horses upon infection by EIAV has been conducted, Therefore, we initiated the first comprehensive ch aracterization of the cellular and humoral immune responses during cli nical progression from chronic disease to inapparent stages of EIAV in fection, Using new analyses of antibody avidity and antibody epitope c onformation dependence that had not been previously employed in this s ystem, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature, During this time frame , EIAV-specific antibody evolved gradually from a population character ized by low avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high Levels, neutralizing activity, and predominantly conformational e pitope specificity, Analyses of the cell-mediated immune response to E IAV revealed CD4(+) and CD8(+) major histocompatibility complex-restri cted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent wit hin 3 to 4 weeks postinfection, temporally correlating with the resolu tion of the primary viremia, After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally i nfected ponies, with some animals having readily detectable CTL activi ty while others had little measurable CTL activity, Thus in contrast t o the initial viremia, it appeared that no single immune parameter cor related with the resolution of further viremic episodes, Instead, immu ne control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system m echanisms to suppress viral replication that effectively functions onl y after the immune system has evolved to a fully mature state 6 to 8 m onths postinfection, These findings strongly imply the necessity for c andidate EIAV and other lentivirus vaccines to achieve this immune sys tem maturation for efficacious immunological control of lentivirus cha llenge.