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Vesicular Stomatitis Virus Glycoprotein Displaying Retrovirus-Like Particles Induce a Type I IFN Receptor-Dependent Switch to Neutralizing IgG Antibodies¹

Patricia Bach^*, Elisabeth Kamphuis^2,*, Bernhard Odermatt, Gerd Sutter, Christian J. Buchholz and Ulrich Kalinke^3,*

^* Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany; Department of Pathology, University Hospital Zürich, Zürich, Switzerland; Division of Virology, Paul-Ehrlich-Institut, Langen, Germany; and Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany

Vesicular stomatitis virus (VSV) infection rapidly induces IFN- that confers initial survival, whereas long-term protection is mediated by neutralizing IgG responses. Because coadministration of IFN- can enhance Ab responses against soluble Ags, we addressed whether virus-induced IFN- also had an impact on the induction of neutralizing Ab responses. To this end, we generated apathogenic retrovirus-like particles (VLP) displaying the VSV gp (VLP-VSV). Reminiscent of live VSV, VLP-VSV induced VSV-neutralizing IgM responses that switched to IgG in a T help-dependent manner. In type I IFN receptor-deficient (IFNAR^–/–) mice, VLP-VSV injection elicited neutralizing IgM, whereas the IgG switch was absent. The lack of subclass switch was associated with a reduced germinal center reaction. Conditional knockout mice with a lymphocyte-specific IFNAR ablation showed normal Ab responses against VLP-VSV, as well as against live VSV. Thus, IFNAR triggering critically promoted the T help-dependent subclass switch of virus-neutralizing Ab responses against VLP-VSV. Interestingly, in the context of VLP-VSV as well as VSV immunization, IFNAR triggering of B lymphocytes did not play a critical role.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the German Research Council (SFB432, B15), the Volkswagen Foundation, and the European Community (PRIOVAX, Contract QLK2-CT-2002-81399).

² Current address: Testing Laboratory for In Vitro-Diagnostics, Paul-Ehrlich-Institut, Langen, Germany.

³ Address correspondence and reprint requests to Dr. Ulrich Kalinke, Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany. E-mail address: kalul{at}pei.de

⁴ Abbreviations used in this paper: VSV, vesicular stomatitis virus; CGG, chicken -globulin; DC, dendritic cell; EGF, epidermal growth factor; FDC, follicular DC; GC, germinal center; int, intermediate; LCMV, lymphocytic choriomeningitis virus; MLV, murine leukemia virus; PNA, peanut hemagglutinin; VLP, retrovirus-like particle; VLP-EGF, EGF-displaying VLP; VLP-VSV, VLP displaying VSV gp; VSV-G, VSV gp; VSV-IND, VSV serotype Indiana; WT, wild type.