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235 CpG Overcomes the Th2 Biased Immune Profile in Schistosoma-Infected Mice to Generate Th1 Type HIV-1-Specific Immune Responses to Remune-Relevance to AIDS Vaccines in Developing Countries
M. Ayash-Rashkovsky1 , Z. Weisman1, G. Borkow1, R. Moss2, and Z. Bentwich1*
1Hebrew Univ. Hadassah Med. Sch., Rehovot, Israel and 2Immune Response Corp., San Diego, CA, USA
Background: The extremely high prevalence of geohelminthic infections in Africa and South East Asia, with dominant Th2 type of immune profile, may undermine the ability to generate potent HIV protective vaccines. The purpose of the present study was to determine whether CpG motifs, could overcome such Th2 bias in Schistosoma-infected mice following immunization with HIV antigens.
Methods: We examined the adjuvant effect of a synthetic CpG ODN (1826) when coadministrated with whole-killed, gp120-depleted HIV-1 antigen(Remune) in Schistosoma mansoni-infected mice 6 weeks after infection with the parasites once the Th2 immune profile is established.
Results: t HIV-1 antigen in incomplete Freund's adjuvant (IFA) combined with CpG ODN stimulated strong antibody responses to core HIV-1 antigen (p24), with 1,000-fold higher titers of IgG2a (indicative of a Th1 response) than immunization with HIV-1 antigen in IFA only (ratio of IgG1/IgG2a = 1 and 50, respectively). Following exposure to HIV-1 antigen, lymph node cells from CpG HIV immunized Schistosoma-infected mice, proliferated 2-fold more and secreted 4- and 1,000-fold higher amount of RANTES (a beta-chemokine) and IFN-gamma, respectively, than cells from mice immunized with HIV-1 antigen alone. The general Th2 immune background was not altered as determined by the ratio of total IgG1/IgG2a antibodies and analysis of cytokines secreted by ConA stimulated lymph node cells. The protective Th2 immune response to Schistosoma was not disrupted, as evidenced by the ratio of anti-Schistosoma IgG1/IgG2a antibodies and by the extremely high levels of specific anti-Schistosoma IgE.
Conclusions: (1) CpG ODN can be used as a Th1 inducing adjuvant in combination with candidate HIV vaccines, when immunizing populations with a strong preexistent Th2 immune profile. (2) This is very relevant to large populations in developing countries where helminthic infections are highly prevalent and Th2 dominant immune profile is present. (3) This approach does not seem to diminish protective anti-parasitic immune responses.
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