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.
Induction of Protective Cytotoxic T Cell Responses in the Presence of High Titers of Virus-neutralizing Antibodies: Implications for Passive and Active Immunization
This work was supported by Swiss National Science Foundation grants 31-32195.91, 31-32179.91, 31-50884.97, and 31-50900.97.
Address correspondence to Peter Seiler, Institute of Experimental Immunology, Department of Pathology, University of Zürich, Schmelzbergstrasse 12, CH 8091 Zürich, Switzerland. Phone: 41-1-255-29-89; Fax: 41-1-255-44-20.
Marie-Anne Bründler's current address is Division de pathologie clinique, centre medical universitaire (C.M.U.), rue Michel-Servet 1, 1211 Geneve 4, Switzerland.
Christine Zimmermann's present address is Institute for Medical Microbiology and Hygiene, Department of Immunology, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany.
Peter Seiler and Marie-Anne Bründler contributed equally to this work.
Peter Seiler, Marie-Anne Bründler, Christine Zimmermann, Doris Weibel, Michael Bruns, Hans Hengartner, Rolf M. Zinkernagel; Induction of Protective Cytotoxic T Cell Responses in the Presence of High Titers of Virus-neutralizing Antibodies: Implications for Passive and Active Immunization . J Exp Med 16 February 1998; 187 (4): 649–654. doi: https://doi.org/10.1084/jem.187.4.649
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