Schistosoma mansoni Tegument Protein Sm29 Is Able to Induce a Th1-Type of Immune Response and Protection against Parasite Infection

Abstract

BackgroundSchistosomiasis continues to be a significant public health problem. This disease affects 200 million people worldwide and almost 800 million people are at risk of acquiring the infection. Although vaccine development against this disease has experienced more failures than successes, encouraging results have recently been obtained using membrane-spanning protein antigens from the tegument of Schistosoma mansoni. Our group recently identified Sm29, another antigen that is present at the adult worm tegument surface. In this study, we investigated murine cellular immune responses to recombinant (r) Sm29 and tested this protein as a vaccine candidate.Methods and FindingsWe first show that Sm29 is located on the surface of adult worms and lung-stage schistosomula through confocal microscopy. Next, immunization of mice with rSm29 engendered 51%, 60% and 50% reduction in adult worm burdens, in intestinal eggs and in liver granuloma counts, respectively (p<0.05). Protective immunity in mice was associated with high titers of specific anti-Sm29 IgG1 and IgG2a and elevated production of IFN-γ, TNF-α and IL-12, a typical Th1 response. Gene expression analysis of worms recovered from rSm29 vaccinated mice relative to worms from control mice revealed a significant (q<0.01) down-regulation of 495 genes and up-regulation of only 22 genes. Among down-regulated genes, many of them encode surface antigens and proteins associated with immune signals, suggesting that under immune attack schistosomes reduce the expression of critical surface proteins.ConclusionThis study demonstrates that Sm29 surface protein is a new vaccine candidate against schistosomiasis and suggests that Sm29 vaccination associated with other protective critical surface antigens is the next logical strategy for improving protection.

Vaccinomics for the Major Blood Feeding Helminths of Humans

“…This finding, however, limits the number of target vaccine antigens to a manageable number. Indeed, where tested, these outer membrane proteins have conferred good levels of protection in mice and are recognized preferentially by antibodies from resistant people in Brazil (Cardoso et al, 2006(Cardoso et al, , 2008Tran et al, 2006). A similar study was conducted using biotinylated S. japonicum, but instead of excising bands from a onedimensional gel for protein extraction, Mulvenna and colleagues (2010) used an off-gel electrophoresis technique to minimize protein loss during sample preparation and subsequently identified orthologues of the S. mansoni-labeled proteins as well as additional membrane spanning proteins of interest (Fig.…”

Schistosomes—proteomics studies for potential novel vaccines and drug targets

“…Interestingly, two of the tegumental proteins detected in proteomic studies, Sm29 and CD63-like protein tetraspanin (Sm-TSP-2), have been recently used in independent experiments as vaccine candidates, causing high reductions of worm burden (>50%) and of liver egg burden (>60%) in animal models [48,49]. Although none of these works has used the proteomic data as a starting point for antigen selection, these results show the potential of tegument proteins as candidates for vaccine development, highlighting the importance of those additional tegument proteins newly detected by proteomics, which were discussed in the previous paragraphs.…”

Factors Associated with Resistance to Schistosoma mansoni Infection in an Endemic Area of Bahia, Brazil

“…antigens, such as Sm22.6, Sm29, Sm21.6, and Sm14, are associated with resistance to infection and/or reduction of morbidity. [9][10][11][12] These particular proteins are found mainly in the tegument of S. mansoni, and induce high levels of IL-4, IL-10, and IFN-g production that exert partial protection against experimental S. mansoni infection. 13 Additionally, a fraction of S. mansoni soluble adult worm antigen (SWAP) known as PIII is able to induce protection against a challenge infection after immunization in a murine model of schistosomiasis.…”