Development of mucosal vaccines for inducing immunity in the female reproductive tract would have profound implications for the prevention of sexually transmitted diseases. Despite numerous efforts, no such vaccines are currently available. Mammalian immune systems sense pathogens through a series of pattern recognition receptors of which the best characterized are Toll-like receptors (TLRs). Activation of TLRs represents the first line of defense and is crucial for linking the innate and the adaptive immune responses.
Recent pioneering works from our group introduce CpG, a TLR9 ligand, as a novel intervention strategy to blunt genital herpes infection and disease in the female genital tract. We could also show that CpG ODN is a potent, and so far the only, vaginal adjuvant capable of eliciting acquired immune protection against a sexually transmitted pathogen.
Another subject of intense research in the group is the development of novel mucosal adjuvants based on use of stimulators of innate immunity e.g., TLR ligands. We have recently developed a potent, rationally designed, immunostimulatory agent based on CpG ODN linked to the non toxic B subunit of cholera toxin (CTB). CTB-CpG was shown to markedly enhance the antigen-specific antibody as well as cell-mediated immune responses against several vaccine antigens. We are also currently investigating the impact of proteoliposome (PL) and PL-derived cochleate structure obtained from Neisseria meningitidis for induction of immunity in the female genital tract against different sexually transmitted pathogens. Studies are underway to explore the immunostimulatory and adjuvant effects of these and other novel candidate adjuvants for induction of immunity against genital herpes and HIV infection in preclinical settings. These studies may provide a preclinical proof-of-concept to introduce a novel approach to counter sexually transmitted diseases in humans.
Harandi, AM. (2004). The potential of immunostimulatory CpG DNA for inducing immunity against genital herpes: Opportunities and challenges. J. Clin. Virol. 30:207.
Tengvall S, Lundqvist A, Eisenberg RJ, Cohen GH, Harandi AM. (2006). Mucosal administration of CpG DNA elicits potent CC and CXC chemokine responses in the vagina and serves as potent Th1-tilting adjuvant for gD2 protein vaccination against genital herpes. J. Virol.. 80:5283.
Adamsson J, Lindblad M, Lundqvist A, Kelly D, Holmgren J, and Harandi AM. (2006). Novel immunostimulatory agent based on CpG oligodeoxynucleotide linked to the non-toxic B subunit of cholera toxin. J. Immunol. 176:4902.