Evaluation of vaccine development againstthe human pathogen, Schistosoma mansoniIntroductionHuman Schistosomiasisis among the neglected tropical disease acknowledged by the World HealthOrganization (WHO) (Fuaad et al., 2015). Estimated by WHO in 2016, at least206.
5 million people have required treatment for schistosomiasis out of whichmore than 88 million people were reported to have been treated worldwide.(World Health Organization, 2017). Humanschistosomiasis (acute or chronic), is a parasitic disease caused by three mainspecies of genus Schistosoma, Schistosoma mansoni, S. japonicum (causesof intestinal/hepatic schistosomiasis) and S.haematobium, results in urogenital schistosomiasis (Merrifield et al., 2016;Walker 2011). The main focus of the systematic review will be on S. mansoni.
Schistosoma mansoni, which is transmitted by Biomphalaria snails, which leads to intestinal and hepaticschistosomiasis in Africa, the Arabian peninsula, and South America (Figure 1) (Merrifieldet al., 2016; WHO, 2017)Life Cycleand TransmissionTheblood-dwelling fluke worms has a cylindrical body, a complex tegument andmature into separate sex adults. The adult worms live within the vein of theirhuman host (Colley et al.
, 2014). This complex life cycle has given theparasites a co-evolution in intricate interplay between the parasite and thesnail or vertebrate host, also between the adult and female worms (Walker2011). Thelife cycle of schistosomes, at fresh water with excreted eggs from infectedhuman urine, faeces or vaginal discharge. On contact with fresh water, the eggsrelease a miracidum. The ciliated miracidium then swims and are in look for anintermediate host snail to start their next stage in their life cycle. Once themiracidium have penetrated the snails they replicate due to asexualreproduction, through this #process the mother and daughter sporocyst stageoccur and finally produce thousands of cercariae (approximately 4-6 weeks afterinfection) (Walker 2011, and Colley et al., 2014).
The cercariae then leave thesnail host seeking a suitable final host. Human infection occur due to cercariaepenetration thought the skin, after infecting the parasite starts to travel bytransforming into parasitic schistosomula by shedding its tail (Walker 2011).The schistosomula slowly migrate in the skin travelling along the pulmonarycapillaries (lung schistosomula) and entering the circulation to migrate todesignated location, S. manosni reside in the mesenteric venules (Walker 2011,Alberto-Silva et al., 2015). Rapid growth begins when the parasite reaches theblood vessels, where the parasite begins the develop into an adolescent stageto sperate sex adults. S.
mansoni, thefirst schistosomula that arrives around day 7, the gut caeca join posteriorlyaround day 15, sex organs develop after approximately 21 days. Around 4 – 5weeks after skin penetration the adult worms start the egg production, wherethe female releases hundreds of eggs per day and continues for up to 15 years(Walker 2011). Thetegument (Figure 2), the outermost surface of intra-mammalian stages of theparasite is the major contributor to the parasite’s survival but is it also avulnerable target for vaccines and drugs. This is the location where thehost-parasite interface occurs (Githui et al., 2009). Adult worms resided inhuman veins import sugar directly across from the bloodstream to their internaltissues using their tegument and transport proteins located on them. Molecularcharacterization techniques have been used to determine the composition andabundance of proteins located on the tegument for have a better understandingof the tegument.
This would help when looking for new drug and possible vaccinetargets in the parasite. Figure 2. Proteins exposed on the outer tegument of adult S.
mansoni. Thetegument of male worm (left) and female worm(right). t. tubercles. ep- excretorypore.
(ClaudineideNascimento Fernandes de Oliveira et al., 2013). Adaptation of Brachi, Borges and Wilson, 2006diagram representing the S. mansoni tegumentand associated cell body- not to scale. The tegument of adult worm consists ofcytoplasmic syncytium with an exclusive double outer tegument membrane. The S.mansoni outer tegument contains twoclosely apposed lipid bilayers, extend over the pitted surface of the tegument,inclusion the spine (Xavier et al.
, 1998). The nullity layered vesicles travelfrom the cell body and discoid bodies though the cytoplasmic channels to thetegument. (Brachi, Borges and Wilson, 2006).
As thecurrent treatment for Human Schistosomiasis, praziquantel (PZQ) is the drug beingused widely due to high cure rate and no significant side effect (Pinto-Almediaet al., 2015), though it is safe and a simple drug to use, the effect againstimmature worms or eggs and preventing of re-infection is negative. There isalso a huge problem relating to the resistance to drugs. PZQ have beenco-administered with albendazole and ivermectin, in areas where these drugshave been used separately for preventive chemotherapy. Recent study conductedby Pinto-Almeida et al., (2015) highlights the involvement of effiux pumps, forinstance members of ATP-binding cassette transport proteins, includingP-glyvcoprotein (P-gp) and multiple drug resistant associate proteins in S.
mansoni resisting to PZQ. Somestudies have shown increased tolerance to PZQ in male worm (Kasinathan et al.,2009 and Kasinathan and Greenberg. 2012), however the results are not replicatedto the female worms, this suggests that the resistance mechanism may bedifferent in the adult worms (Pinto-Almeida et al.
, 2015).Thisfactor alone is alarming and pushes forward the need for vaccine, whether toprevent or as therapeutic against human schistosomiasis. Even though there areno vaccines available for human schistosomiasis so far, the number of studiesconducted up to now are showing possible targets and vaccine candidates with greatpotential. Tretraspanin (an example aspossible candidate)Thereare over 100 possible vaccine candidates that have been identified. Howeveronly hand few of molecules, S.
mansoni fattyacid binding protein (Sm14), S. mansoni tetrspanin(Sm-TSP-2) have entered human clinical trials with Smp80 (calpain) undergoingtesting in non-human primates. (Tebeje et al.
, 2016)Thetetranspanin family of integral membrane proteins seems to be in abundant inthe tegument of schistosomes, and studies done on mouse vaccine models suggeststhat this gamily of membrane proteins offer promising results of possible schistosomiasisvaccine (Loukas, Tran and Pearson, 2007)Tetrapsnainsengage in wide range of specific molecular interactions that occur though theformation of tetraspanin-enriched microdomains. They are family of membraneproteins found in all multicellular eukaryotes. Tetraspanins are superfamily ofproteins with four transmembrane domains with characteristic of structuralfeatures (Andreu and Yáñez-Mó, 2014).