Background:  Development of vaccines capable of preventing the transmission or limiting the severity of sexually transmitted viruses, such as HIV, will likely be dependent on the induction of a potent long-lasting mucosal immune response in the genital tract. In this study, we evaluated the immune responses and protection elicited with inactivated gp120-depleted HIV-1 immunogen, REMUNE, alone or in combination with the mucosal adjuvant, CpG oligodeoxynucleotides (ODN) in the genital tract of intranasally immunized mice.

Methods:  Female mice were immunized intranasally with REMUNE alone or mixed with CpG ODN or control non-CpG ODN.  The production of anti-p24 IgA and IgG in vaginal washes and serum was determined by ELISA.  HIV-specific proliferative responses, IFN-g and b-chemokine production were evaluated following in vitro restimulation.  The frequency of HIV-1 antigen-stimulated interferon-g (IFN-g)-producing cells was determined by ELISPOT assay.  In vivo protection of immunized mice was assessed following intravaginal (IVAG) challenge with recombinant vaccinia viruses expressing HIV-1 gag.

Results:  Mice immunized with REMUNE plus CpG ODN had significantly enhanced levels of anti-p24 IgA antibodies in serum and vaginal washes.  Titres of p24-specific IgA antibodies at estrus and IgG antibodies at diestrus were found to be highest on average in the genital tract of REMUNE plus CpG ODN immunized mice and was also shown to be dependent on the dose of HIV-1 immunogen. Splenocyte production of IFN-g and b-chemokines, which are known to inhibit the use of the CCR5 co-receptor by HIV, were also significantly higher in mice immunized with REMUNE plus CpG.  Moreover, the immunization provided protection against IVAG challenge with recombinant vaccinia virus expressing HIV-1 gag.

Conclusions:  These results indicate that intranasal immunization with REMUNE plus immunostimulatory CpG ODN can induce potent immune responses in the murine genital tract capable of protection against local IVAG challenge.