Sm16, A Schistosoma mansoni Immunomodulatory Protein, Fails to Elicit a Protective Immune Response and Does Not Have an Essential Role in Parasite Survival in the Definitive Host.

Wilma Patrícia De Oliveira Santos Bernardes,Marina De Moraes Mourão,Gardênia Braz Carvalho,Aline Thaynara De Moura Coelho,Rosy Iara Maciel De Azambuja Ribeiro,Sueleny Silva Ferreira Teixeira,Isabela Thamara Sabino Dutra,Cristina Toscano Fonseca,Rosiane Aparecida Da Silva-Pereira,Juliano Michel De Araújo,Clarice Carvalho Alves

doi:10.1155/2019/6793596

Wilma Patrícia De Oliveira Santos Bernardes, Marina De Moraes Mourão + Show 9 more

Open Access

https://doi.org/10.1155/2019/6793596

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Abstract

Sm16 is an immunomodulatory protein that seems to play a key role in the suppression of the cutaneous inflammatory response during Schistosoma mansoni penetration of the skin of definitive hosts. Therefore, Sm16 represents a potential target for protective immune responses induced by vaccination. In this work, we generated the recombinant protein rSm16 and produced polyclonal antibodies against this protein to evaluate its expression during different parasite life-cycle stages and its location on the surface of the parasite. In addition, we analyzed the immune responses elicited by immunization with rSm16 using two different vaccine formulations, as well as its ability to induce protection in Balb/c mice. In order to explore the biological function of Sm16 during the course of experimental infection, RNA interference was also employed. Our results demonstrated that Sm16 is expressed in cercaria and schistosomula and is located in the schistosomula surface. Despite humoral and cellular immune responses triggered by vaccination using rSm16 associated with either Freund's or alum adjuvants, immunized mice presented no reduction in either parasite burden or parasite egg laying. Knockdown of Sm16 gene expression in schistosomula resulted in decreased parasite size in vitro but had no effect on parasite survival or egg production in vivo. Thus, our findings demonstrate that although the vaccine formulations used in this study succeeded in activating immune responses, these failed to promote parasite elimination. Finally, we have shown that Sm16 is not vital for parasite survival in the definitive host and hence may not represent a suitable target for vaccine development.

Highlights

Schistosomiasis is a neglected tropical disease with an important impact on public health [1]
In order to obtain recombinant form of Sm16 (rSm16), we choose to express the fragment of the Sm16 protein corresponding to amino acids 23-90 in an E. coli system (Figure 1(a))
The His-tag fused to rSm16 was recognized by a monoclonal 6x-His-tag antibody, indicating the correct expression of 15 kDa recombinant protein from the designed gene sequence (Figure 1(c))

Summary

Introduction

Schistosomiasis is a neglected tropical disease with an important impact on public health [1]. The development of an effective vaccine formulation against the disease would help to control its transmission [2, 3]. This is hampered by the complexity of both the parasite and its life cycle [4, 5], as well as by the poor knowledge regarding the biological. Journal of Immunology Research function of vaccine target antigens, and the mechanisms and components of the host’s immune system involved in parasite elimination [6]. Though the host’s skin contains many cells that can respond upon parasite activation, schistosomes have evolved several mechanisms to evade host immune responses. Immune modulatory proteins secreted by the parasite represent an interesting target for the hosts’ protective immune response induced by immunization

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Conclusion