Human Immune Responses to <em>Schistosoma mansoni</em> Vaccine Candidate Antigens

Amélia de Jesus

I Araújo

Olívia Bacellar

Andréa Magalhães

Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Bahia, Brazil^{; Department of Microbiology, Immunology and Parasitology, Cornell University College of Veterinary Medicine, Ithaca, New York}^{; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts}^{; and Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland}⁴

^{Corresponding author. Mailing address: Serviço de Imunologia, Hospital Universitário Prof. Edgard Santos, Universidade Federal da Bahia, Bahia CEP 40110-160, Brazil. Phone: (55-71) 2377353. Fax: (55-71) 2457110. E-mail:}rb.abfu@ragde.

^Deceased.

Received 1999 Jul 26; Revisions requested 1999 Oct 19; Accepted 2000 Feb 16.

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-γ], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-γ 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]).

Abstract

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-γ) 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, 68–70, 74). The World Health Organization (WHO) has selected six of these antigens for further in vitro studies with PBMC from subjects in areas of endemicity for schistosomiasis. The present study shows the immunological responses of subjects from an area where schistosomiasis is endemic to four of these antigens: paramyosin (49), irradiation-associated vaccine antigen (IrV-5) (68), triose phosphate isomerase (TPI) (32, 61), and S. mansoni 23-kDa antigen (Sm-23) (31). The immunological responses of subjects who, though exposed to contaminated water, appear on the basis of negative stool examinations to be uninfected were compared to those of infected patients with similar degrees of contaminated water exposure.

ACKNOWLEDGMENTS

This study was supported by UNDP/WORLD BANK/WHO Special Programme for Research in Tropical Disease (TDR), grant 940687; by Programa de Núcleos de Excelência (PRONEX); and by TMRC, grant AI 30639. Edgar M. Carvalho is senior investigator of the Brazilian Research Council (CNPq).

We thank Antonio de Souza and Sonia de Souza for their dedicated work in the area of endemicity. We also thank Elbe Myrtes and Jackson Lemos for secretarial assistance.

ACKNOWLEDGMENTS

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