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233 Mucosal Immunization with Whole-Killed Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Plus CpG ODN Increases IgA and Immune Responses in the Genital Tract
N. Dumais*1, R. B. Moss2, H. L. Davis3, and K. L. Rosenthal1
1Ctr. for Gene Therapeutics, McMaster Univ., Hlth. Sci. Ctr., Hamilton, Ontario, Canada; 2The Immune Response Corp., Carlsbad, CA, USA; and 3Coley Pharmaceutical Group, Ottawa, Canada
Objective: 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 potent long-lasting mucosal immune response in the genital tract. In this study, we evaluated the immune response elicited by the whole-killed 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: Mice were immunized intranasally (I.N.) with Remune alone or mixed with CpG ODN or control non-CpG ODN. The production of anti-p24 IgA and IgG in vaginal washes was determined by ELISA. HIV-specific proliferative responses and IFN-gamma and beta-chemokine production were evaluated following in vitro restimulation, and the frequency of HIV-1 antigen-stimulated IFN-gamma-producing cells was determined by ELISPOT assay. Immunized mice were also challenge intravaginally (IVAG) with a recombinant vaccinia virus expressing HIV-1 gag.
Results: The immunization of mice with the whole-killed HIV-1 plus CpG ODN significantly enhanced the level of anti-p24 IgA antibodies in mice 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 were also shown to be dependent on the dose of HIV-1 immunogen. Production of IFN-gamma and beta-chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV, were also significantly higher in mice immunized with the combination Remune plus CpG. Moreover, the immunization provided protection against IVAG challenge with the 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 that protect against local IVAG challenge.
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