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The Mucosal Adjuvant Effect of -Galactosylceramide for Induction of Protective Immunity to Sexually Transmitted Viral Infection¹

Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Development of mucosal adjuvants to generate immunity in the female genital tract may have important implications for the development of vaccines to counter sexually transmitted infections. -Galactosylceramide (-GalCer) is presented by CD1d molecule on APCs to invariant V14⁺ NKT (iNKT) cells, which upon activation rapidly produce large amounts of immunomodulatory cytokines, leading to activation of a variety of innate and adaptive immune cells. Here, we assessed whether -GalCer could act as a mucosal adjuvant for induction of protective immunity against genital herpes. We found that intranasal immunization with HSV-2 glycoprotein D (gD) in combination with -GalCer elicits strong systemic gD-specific IgG Ab response as well as lymphoproliferative response with a mixed Th1/Th2 cytokine profile in the spleen, mediastinal lymph nodes, and genital lymph nodes. Importantly, such an immunization scheme conferred complete protection against an otherwise lethal vaginal HSV-2 challenge. We could also show that intravaginal immunization with gD plus -GalCer generates potent gD-specific lymphoproliferative and IFN- responses in the genital lymph nodes and spleen. Furthermore, the vaginally immunized mice developed a strong systemic and mucosal IgG Ab response and protection against vaginal HSV-2 challenge. The mucosal adjuvant effect of -GalCer was found to be mediated via CD1d molecule and appeared to be independent of the usage of the adaptor molecule MyD88. To our knowledge, this is the first report on the mucosal adjuvant effect of -GalCer for induction of protective immunity against a sexually transmitted pathogen.

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 study was supported by the Swedish Research Council Medicine (VR), the Swedish International Development Cooperation Agency, the Åke Wiberg Foundation, the Swedish Society of Medicine, and the Wilhelm and Martina Lundgren foundation.

² Address correspondence and reprint requests to Dr. Ali M. Harandi, Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 7A, 40530 Gothenburg, Sweden. E-mail address: ali.harandi{at}microbio.gu.se

³ Abbreviations used in this paper: gB, glycoprotein B; -GalCer, -galactosylceramide; gD, glycoprotein D; gLN, genital lymph node; i.n., intranasal(ly); iNKT, invariant V14⁺ NKT; i.vag., intravaginal(ly); MdLN, mediastinal lymph node; ODN, oligodeoxynucleotide.