Schistosoma mansoni ex vivo lung-stage larvae excretory-secretory antigens as vaccine candidates against schistosomiasis

Zoology Department, Faculty of Science, Cairo University, Cairo 12613, Egypt.
Vaccine (Impact Factor: 3.49). 01/2009; 27(5):666-73. DOI: 10.1016/j.vaccine.2008.11.039
Source: PubMed

ABSTRACT Schistosoma mansoni lung-stage larvae are known to be the major target of innate and acquired immunity to schistosomiasis. Lung schistosomula cytosolic or surface membrane antigens are hidden, entirely inaccessible to the host immune system, and hence are not particularly important as vaccine candidates. Conversely, excretory-secretory (E-S) products released from intact, viable, elongated, and contractile schistosomula are ideal potential vaccines, as such molecules can readily play a central role in the induction of local primary and memory immune response effectors that would directly target, surround, and pursue the larvae while negotiating the lung capillaries. Therefore, 6-day-old ex vivo larvae were isolated from mouse or hamster lung cells and used for generation of E-S products, which were shown to elicit strong immune responses and significant (P<0.05) protection against challenge infection in BALB/c mice. Proteomic analysis of E-S molecules following 10x concentration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis identified peptides related to innumerable host and about 15 S. mansoni-specific proteins. Selected S. mansoni-specific E-S peptides prepared in a multiple antigen peptide (MAP) or recombinant form were shown to stimulate considerable specific antibody response and peripheral blood mononuclear cell expression of mRNA for several cytokines in immunized C57BL/6 and BALB/c mice. However, highly significant (P<0.05 to <0.005) reduction in challenge infection worm burden and egg load was recorded only when the immunization conditions in test mice provided the S. mansoni antigen-specific T helper (Th) type response milieu favorable for each immunogen. That was polarized Th1 for S. mansoni aldolase and thioredoxin peroxidase 1 MAPs, polarized Th2 for recombinant 14-3-3-like protein, mixed Th1/Th17 for calpain MAP, and mixed Th1/Th2 for recombinant p18 protein. The findings together indicated that the immune responses issue is as critical as the nature and source of the antigen for the development of vaccine against schistosomiasis.

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    • "After schistosome cercariae penetrate the skin and transform into schistosomula, they enter the vasculature and migrate (depending on species) to the portal or bladder vessels via the lungs. The first 3 to 5 days of this migratory process between the skin and the lungs is thought to represent the most susceptible stage to antibody-mediated killing (El Ridi and Tallima, 2009; McManus and Loukas, 2008; Mountford et al., 1995). "
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    • "This represents a mechanism of immune evasion utilized by hemo-helminths to evade the protective host immune response [6,8–10]. This novel protein, calpain, has two subunits, the larger of which, Sm-p80, was shown in our previous studies [9,11–15] and of other investigators [16] [17] [18] [19] to have a great potential as relevant vaccine antigen for reduction of the morbidity associated with both Schistosoma mansoni [4] and Schistosoma japonicum [17] because of its pronounced antifecundity and anti-worm effects in mice. In the present study we have examined the prophylactic and antifecundity efficacy of an Sm-p80-based DNA vaccine formulation against S. mansoni in a nonhuman primate model. "
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