c Schistosome infection induces significant T helper type 2 (Th2) and anti-inflammatory immune responses and has been shown to negatively impact vaccine efficacy. Our goal was to determine if the administration of schistosome soluble egg antigens (SEA) would negatively influence the induction of cytotoxic T lymphocyte (CTL) and Th1-type T cell responses to an HIV candidate vaccine in the Th1-biased C57BL/6 mouse strain. Initial experiments failed, as we were unable to detect any response to the defined class I epitope for HIV-1 IIIB Gag. Therefore, we initiated an epitope mapping study to identify C57BL/6 (H-2 b ) T cell epitopes in HIV-1 IIIB Gag in order to perform the experiments. This analysis defined two previously unreported minimal class I H-2 b and class II I-A b epitopes for HIV-1 IIIB Gag. The newly defined HIV-1 IIIB Gag epitopes were used to evaluate the influence of SEA on the generation of CTL and Th1-type HIV-1 IIIB Gag responses. Surprisingly, in contrast to our hypothesis, we observed that the coadministration of SEA with a Listeria monocytogenes vector expressing HIV-1 IIIB Gag (Lm-Gag) led to a significantly increased frequency of gamma interferon (IFN-␥)-producing CD8؉ and CD4 ؉ T cells in C57BL/6 mice compared to mice immunized with Lm-Gag only. These observations suggest that SEA contains, in addition to Th2-type and immune-suppressive molecules, substances that can act with the Lm-Gag vaccine to increase CTL and Th1-type vaccine-specific immune responses.V accines for human immunodeficiency virus (HIV), tuberculosis, and malaria are in development or in clinical trials. The greatest incidence of each of these diseases is in sub-Saharan Africa, where helminth infection is endemic (1, 2). Helminth parasites bias immune responses to the CD4 ϩ Th2 type and can be immune suppressive (3-10). To evaluate the influence of helminth infection on vaccines, we can evaluate the ability to induce vaccine-specific immune responses in helminth-infected recipients or in recipients who have been treated with immune-biasing helminth antigens (11-13).Schistosomiasis is a helminth parasitic disease that affects Ͼ200 million people worldwide and is listed by the World Health Organization (WHO) as the second leading parasitic disease, after malaria (14). Infection occurs when cercariae that emerge from infected snail intermediate hosts contact and penetrate the skin of the vertebrate host. Larval parasites migrate and mature into adult male and female worms that mate and produce eggs (4, 6). Eggs that become lodged within host tissues are largely responsible for Th2 biasing of the host immune system and induction of antiinflammatory responses (3,4,6,15,16).Immune biasing induced by schistosome infection has been shown to reduce vaccine efficacy in both laboratory and clinical settings (8,11,17,18). Specifically, helminth infection has been shown to suppress immune responses to a Th1-type vaccine and impair the expansion of pathogen-specific cytotoxic CD8ϩ T cell (cytotoxic T lymphocyte [CTL]) responses (18)(19)(...