J. Exp. Med., Volume 187, Number 4, February 16, 1998 649-654

BRIEF DEFINITIVE REPORT:
Induction of Protective Cytotoxic T Cell Responses in the Presence of High Titers of  Virus-neutralizing Antibodies: Implications for Passive and Active Immunization

By Peter Seiler,^* Marie-Anne Bründler,^* Christine Zimmermann,^* Doris Weibel,^* Michael Bruns, Hans Hengartner,^* and Rolf M. Zinkernagel^*

From the ^* Institute of Experimental Immunology, Department of Pathology, University of Zürich, CH-8091 Zürich, Switzerland; and the  Heinrich Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, D-20251 Hamburg, Germany

The effect of preexistent virus-neutralizing antibodies on the active induction of antiviral T cell responses was studied in two model infections in mice. Against the noncytopathic lymphocytic choriomeningitis virus (LCMV), pretreatment with neutralizing antibodies conferred immediate protection against systemic virus spread and controlled the virus below detectable levels. However, presence of protective antibody serum titers did not impair induction of antiviral cytotoxic T lymphocyte (CTL) responses after infection with 10² PFU of LCMV. These CTLs efficiently protected mice independent of antibodies against challenge with LCMV-glycoprotein recombinant vaccinia virus; they also protected against otherwise lethal lymphocytic choriomeningitis caused by intracerebral challenge with LCMV-WE, whereas transfused antibodies alone did not protect, and in some cases even enhanced, lethal lymphocytic choriomeningitis. Against the cytopathic vesicular stomatitis virus (VSV), specific CTLs and Th cells were induced in the presence of high titers of VSV-neutralizing antibodies after infection with 10⁶ PFU of VSV, but not at lower virus doses. Taken together, preexistent protective antibody titers controlled infection but did not impair induction of protective T cell immunity. This is particularly relevant for noncytopathic virus infections since both virus-neutralizing antibodies and CTLs are essential for continuous virus control. Therefore, to vaccinate against such viruses parallel or sequential passive and active immunization may be a suitable vaccination strategy to combine advantages of both virus-neutralizing antibodies and CTLs.

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