Current status and future prospects of protein vaccine candidates against Schistosoma mansoni infection

Abstract

Schistosomiasis is an acute and chronic tropical parasitic disease caused by blood dwelling worm of the genus Schistosoma. It is the most destructive disease globally and is a major cause of morbidity and mortality for developing countries. Three main species of schistosomes infect human beings from which S. mansoni is the most common and widespread. Over the last several decades, chemotherapy using praziquantel has been a commonly used strategy for the treatment and control of schistosomiasis. However, control programs focused exclusively on chemotherapy have been challenging because of the frequency and rapidity of reinfection and these programs were expensive. Thus, new schistosomiasis control strategies will be needed. Vaccination strategy would be an ideal tool for a significant and sustainable reduction in the transmission and disease burden of schistosomiasis. An effective anti schistosome vaccine would greatly contribute to decreasing schistosomiasis-associated morbidity via protective immune responses leading to reduced worm burdens and decreased egg production. Vaccine development is a long process that can take decades. There have been three candidate vaccines that have been produced by Good Manufacturing Procedure and entered human clinical trials for S. mansoni are Sm14, SmTSP-2, and Sm-p80. Other candidates that are in pre-clinical trials at various stages include paramyosin, Sm29, SmKI-1, and Sm23. Since the growth of several new technologies, including genomics, transcriptomics, microarrays, immunomic profiling, and proteomics, have helped in the identification of promising new target schistosome antigens. Therefore, this review considers the present status of protein vaccine candidates against Schistosoma mansoni and provides some insight on prospects vaccine design and discovery.

T Cell Peptides Derived from Invasive Stages of Schistosoma mansoni as Potential Schistosomiasis Vaccine

“…The SmGSP 15 amino acid-long T cell peptide was obtained from the Smp_136730 sequence, a peptidase from the A1 subfamily. Peptidases have been widely used for designing linear and conformational cathepsin-derived epitopes [ 43 , 44 , 45 ]. SmTNP belongs to an N-acetyl galactosaminyl transferase involved in o-glycan biosynthesis using calcium and magnesium ions as cofactors.…”

A comprehensive and critical overview of schistosomiasis vaccine candidates

“…The fusion of Sm29 with Sm14, designated as Sm14/29 alone or combined with polyinosinic-poly cytidylic acid [poly (I:C)] adjuvant elicited significant reduction of adult worm burden by 48.4% and 44.7%, liver egg burden by 82.8% and 73.5, intestinal egg count by 72.8% and 76.6%, respectively, in Swiss albino mice (Mossallam et al 2015 ; Eyayu et al 2020 ). Similarly, Sm29 fused with Sm-TSP-2 resulted in reduction (22–35%) of worm burden, with an elevated level of IgG1 and IgG2 antibodies, IFN-γ and TNF-α in C57BL/6 mice (Pinheiro et al 2014 ).…”

“…It protects worms from complement-mediated damage by binding human C8 and C9 proteins, preventing complement activation at the terminal stage, in vitro and in vivo. Paramyosin protein either native or in a recombinant form was considered a vaccine candidate for protection against schistosomiasis (Gobert and McManus 2005 ; Deng et al 2007 ; McManus and Loukas 2008 ; Jiz et al 2015 ; Eyayu et al 2020 ). Additionally, paramyosin peptides were recognized by T cells of humans resistant to schistosomiasis infection and reinfection (Fonseca et al 2005 ; Eyayu et al 2020 ).…”

“…Furthermore, immunization of Swiss albino mice three times with purified Sm97 induced 44.1%, 59.1%, and 61% reduction in worm burden, intestinal egg loads, and granuloma size, respectively. The protective immunity was associated with high levels of specific anti-Sm97 IgG1 and IgG2 antibodies (Diab and Aly 2011 ; Eyayu et al 2020 ).…”

Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

“…Because the development of a schistosomiasis vaccine has proved challenging (10,11), the treatment and control of schistosomiasis continue to depend, on the almost 50-year-old drug, praziquantel (PZQ) (12,13). PZQ is generally effective against adult and schistosomula stages of all schistosome species and is well tolerated, causing only mild and transient side effects (14,15).…”