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Nasal and skin delivery of IC31-adjuvanted recombinant HSV-2 gD protein confers protection against genital herpes

Journal article
Authors Ben Wizel
Josefine Persson
Karolina Thörn
Nagy Eszter
Ali M Harandi
Published in Vaccine
Volume 30
Issue 29
Pages 4361-4368
ISSN 0264-410X
Publication year 2012
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 4361-4368
Language en
Links dx.doi.org/10.1016/j.vaccine.2012.0...
Keywords Herpes simplex virus; Genital immunity; Adjuvant; Mucosal vaccine; Immunization routes; Type 1/type 2 immune responses
Subject categories Microbiology in the medical area

Abstract

Genital herpes caused by herpes simplex virus type 2 (HSV-2) remains the leading cause of genital ulcers worldwide. Given the disappointing results of the recent genital herpes vaccine trials in humans, development of novel vaccine strategies capable of eliciting protective mucosal and systemic immune responses to HSV-2 is urgently required. Here we tested the ability of the adjuvant IC31 in combination with HSV-2 glycoprotein D (gD) used through intranasal (i.n.), intradermal (i.d.), or subcutaneous (s.c.) immunization routes for induction of protective immunity against genital herpes infection in C57BL/6 mice. Immunization with gD plus IC31 through all three routes of immunization developed elevated gD-specific serum antibody responses with HSV-2 neutralizing activity. Whereas the skin routes promoted the induction of a mixed IgG2c/IgG1 isotype profile, the i.n. route only elicited IgG1 antibodies. All immunization routes were able to induce gD-specific IgG antibody responses in the vaginas of mice immunized with IC31-adjuvanted gD. Although specific lymphoproliferative responses were observed in splenocytes from mice of most groups vaccinated with IC31-adjuvanted gD, only i.d. immunization resulted in a significant splenic IFN-response. Further, immunization with gD plus IC31 conferred 80–100% protection against an otherwise lethal vaginal HSV-2 challenge with amelioration of viral replication and disease severity in the vagina. These results warrant further exploration of IC31 for induction of protective immunity against genital herpes and other sexually transmitted infections.

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