Schistosoma mansoni Soluble Egg Antigens Enhance Listeria monocytogenes Vector HIV-1 Vaccine Induction of Cytotoxic T Cells

Abstract

Vaccines are an important public health measure for prevention and treatment of diseases. In addition to the vaccine immunogen, many vaccines incorporate adjuvants to stimulate the recipient's immune system and enhance vaccine-specific responses. While vaccine development has advanced from attenuated organism to recombinant protein or use of plasmid DNA, the development of new adjuvants that safely increase immune responses has not kept pace. Previous studies have shown that the complex mixture of molecules that comprise saline soluble egg antigens (SEA) from Schistosoma mansoni eggs functions to promote CD4 ؉ T helper 2 (Th2) responses. Therefore, we hypothesized that coadministration of SEA with a Listeria vector HIV-1 Gag (Lm-Gag) vaccine would suppress host cytotoxic T lymphocyte (CTL) and T helper 1 (Th1) responses to HIV-1 Gag epitopes. Surprisingly, instead of driving HIV-1 Gag-specific responses toward Th2 type, we found that coadministration of SEA with LmGag vaccine significantly increased the frequency of gamma interferon (IFN-␥)-producing Gag-specific Th1 and CTL responses over that seen in mice administered Lm-Gag only. Analysis of the functionality and durability of vaccine responses suggested that SEA not only enlarged different memory T cell compartments but induced functional and long-lasting vaccine-specific responses as well. These results suggest there are components in SEA that can synergize with potent inducers of strong and durable Th1-type responses such as those to Listeria. We hypothesize that SEA contains moieties that, if defined, can be used to expand type 1 proinflammatory responses for use in vaccines.

Schistosoma mansoni Soluble Egg Antigens Enhance T Cell Responses to a Newly Identified HIV-1 Gag H-2bEpitope

“…Evaluation of the influence of SEA on the generation of CD4 ϩ and CD8 ϩ T cell responses of Lm-Gag-vaccinated C57BL/6 mice demonstrated that similar to our recent study (24), the administration of SEA with Lm-Gag significantly increased the level of Gag-specific CTL effectors compared to those in mice vaccinated with Lm-Gag alone (Fig. 3D).…”

“…Together, the results presented here and in our recent study (24) show that SEA functioned counterintuitively when administered with the Lm-Gag vaccine, stimulating CTL responses rather than suppressing them. Although it is well known that Listeria is a potent inducer of CD8 ϩ immunity, the specific mechanism(s) by which Listeria vector vaccines can both overcome the immunosuppressive environment of chronic helminth infection (12,13) as well as be adjuvanted by SEA is currently being investigated.…”

“…Thus, our study suggests that for the Lm-Gag vaccine, SEA acts as a CTL adjuvant in C57BL/6 mice, more prone to Th1-type responses, and in BALB/c mice, more prone to Th2-type responses (Fig. 3) (24). We are currently examining if the observed enhancement is simply due to the host immune response to any foreign antigen prior to vaccination with Lm-Gag or is an SEA-specific observation.…”

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

“…The high levels of IFNγ observed would play a role in stimulating the B cells to produce IgG [49] which is important for effective HPV vaccine responses [51]. There is also evidence that SEA from the eggs released during a S. mansoni infection also stimulated the production of proinflammatory cytokines [52]. The findings of this study indicates that a chronic S. mansoni infection or previous exposure to schistosomiasis does not down-regulate Th1 cellular responses to HPV Vaccine.…”

“…The burden of cervical cancer in Sub-Saharan Africa has been steadily increasing and this had led to the introduction and testing of HPV vaccines in Africa [2][3][4][5][6]. Currently, three licensed vaccines against HPV are available; the quadrivalent vaccine Gardasil which provides protection against HPV 6,11,16,18, bivalent vaccine Cervarix which confers protection against the 2 variants, HPV 16 and HPV 18 [7] and a nanovalent vaccine Gardasil9 which protects against HPV 16,18,31,33,45,52 and 58 subtypes [8,9]. These vaccines contain virus-like-particles (VLPs) consisting of the L1 capsid protein.…”