INDUCTION OF PROTECTIVE CYTOTOXIC T-CELL RESPONSES IN THE PRESENCE OFHIGH TITERS OF VIRUS-NEUTRALIZING ANTIBODIES - IMPLICATIONS FOR PASSIVE AND ACTIVE IMMUNIZATION

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infec tions in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred imme diate protection against systemic virus spread and controlled the viru s below detectable levels. However, presence of protective antibody se rum titers did not impair induction of antiviral cytotoxic T lymphocyt e (CTL) responses after infection with 10(2) PFU of LCMV. These CTLs e fficiently protected mice independent of antibodies against challenge with LCMV-glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intra cerebral challenge with LCMV-WE, whereas transfused antibodies alone d id not protect, and in some cases even enhanced, lethal lymphocytic ch oriomeningitis. Against the cytopathic vesicular-stomatitis virus (VSV ), specific CTLs and Th cells were induced in the presence of high tit ers of VSV-neutralizing antibodies after infection with 10(6) PFU of V SV, but not at lower virus doses. Taken together, preexistent protecti ve antibody titers controlled infection but did not impair induction o f protective T cell immunity. This is particularly relevant for noncyt opathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccina te against such viruses parallel or sequential passive and active immu nization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.