Human Immune Responses toSchistosoma mansoniVaccine Candidate Antigens

Abstract

To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n ‫؍‬ 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP-and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-␥], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-␥ levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3-and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio ‫؍‬ 11.2 [95% confidence interval, 2.7 to 45.8]).Schistosomiasis is a chronic parasitic infection that affects 200 million people in Africa, South America, and Asia (35). Although treatment of infected people with schistosomicidal drugs has in part controlled the morbidity of the disease, transmission is largely unaltered (3,5,24). The possibility of a schistosomiasis vaccine as an additional measure to control the disease arose from the fact that the parasite does not multiply in human beings and that reduction of infection levels by schistosomicidal drugs reduces the prevalence of severe forms of the disease. Moreover, in experimental models, partial immunity can be induced by vaccination with irradiated cercariae or specific antigens (2,11,14,26,36,37,58,59). Immunological studies of subjects from areas of endemicity have demonstrated a naturally occurring resistance to reinfection (4, 19, 22-25, 27, 28). Both high levels of specific immunoglobulin E (IgE) in sera and gamma interferon (IFN-␥) in antigen-stimulated peripheral blood mononuclear cell (PBMC) cultures were associated with resistance to reinfection (1,22,24,25,27,28,56,57). These data suggest the participation of immunological mechanisms in human resistance to Schistosoma mansoni infection, with mixed cellular and humoral responses.Several S. mansoni antigens have been identified and tested in experimental models, with the induction of variable levels of protection against infection (11,32,49,59,61,(68)...

Recombinant tegumental protein Shistosoma japonicum very lowdensity lipoprotein binding protein as a vaccine candidate against Schistosoma japonicum

“…In addition, it plays a vital role in acquisition of host derived nutrients, including carbohydrates, amino acids, and lipids (Abath & Werkhauser 1996, Jones et al 2004. Along with other key molecules, tegument associated antigens of schistosomes have been investigated as targets of protective immune responses in murine hosts and for defining antibody and cytokine correlates of apparent resistance and susceptibility in human populations, a key approach to establishing the protective potential of a vaccine candidate (Ribeiro de Jesus et al 2000, Acosta et al 2002, Al-Sherbiny et al 2003, McManus & Bartley 2004, Bergquist et al 2005. Since SVLBP appears to have VLDL binding activity and to locate prominently on the tegument and sub-tegument of adult male schistosomes, SVLBP may play a key role in lipid acquisition by S. japonicum (Fan et al 2003).…”

Identification of paramyosin T cell epitopes associated with human resistance toSchistosoma mansonireinfection

“…S. mansoni paramyosin is strongly recognized by sera of individuals naturally resistant to infection and it also induced high levels of IFN-γ production by peripheral blood mononuclear cells (PBMC) from these individuals [11,12]. Paramyosin also induced significant lymphocyte proliferation and interleukin (IL-2) and IL-5 production in individuals resistant to S. mansoni reinfection [13].…”

“…PBMC of 14% of individuals in this study did not proliferate in response to paramyosin peptides (data not shown). Para (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) was the most promiscuous peptide according to the proliferative responses. PBMC from 20% of the individuals tested proliferated in response to this epitope ( Table 2).…”

Structure–function analysis of apical membrane‐associated molecules of the tegument of schistosome parasites of humans: prospects for identification of novel targets for parasite control

“…In the liver, a male parasite will mate with a female and carry her to mesenteric or pelvic circulation, the final destination being parasite species specific (Wilson, 2009). It was shown that infection of humans with live, RA parasites led to strong protection against subsequent challenge infections with normal cercariae (Correa-Oliveira et al, 2000;Ribeiro de Jesus et al, 2000). Vaccination of animal models with RA cercariae has thus led to an adult worm burden reduction in experimental schistosomiasis of 60-70% (Bickle et al, 1979a,b; CauladaBenedetti et al, 1991;Coulson et al, 1998;McManus, 1999;Dillon et al, 2008).…”