Schistosoma mansoni: vaccination with adult worm antigens.

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequality, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although chemotherapy is capable of reducing morbidity in humans, rapid re-infection demonstrates that the impact of drug treatment on transmission control or disease elimination is marginal. In addition, despite more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic, open knowledge innovation that has successfully completed phase I and phase IIa clinical trials, with Phase II/III trials underway in the African continent, to be followed by further trials in Brazil. The discovery and experimental phases of the development of this vaccine gathered a robust collection of data that strongly supports the ongoing clinical phase. This paper reviews the development of the Sm14 vaccine, formulated with glucopyranosyl lipid A (GLA-SE), from the initial experimental developments to clinical trials including the current status of phase II studies.

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Current Status of the Sm14/GLA-SE Schistosomiasis Vaccine: Overcoming Barriers and Paradigms towards the First Anti-Parasitic Human(itarian) Vaccine

In previous studies it was shown that the recombinant molecule, r-Sm14, induces high levels of protection against Schistosoma mansoni infection in two outbred animal models and immune crossprotection against infection by Fasciola hepatica in Swiss outbred mice. r-Sm14 was derived from a living worm extract, called SE, and is being developed as the molecular basis of an anti-helminth bivalent vaccine against the two parasites, for medical and veterinary application. Present data refer to SDS-PAGE and Western Blotting analysis of four different preparations of S. mansoni adult worms focusing Sm14 identification. The extracts correspond to the initial fraction of the SE extraction process, containing products released by living worms (SEi); SE2, reextraction of adult worms in PBS; and SE of separated male and female adult worms. In all extracts it was possible to detect the component of 14 kDa, that was recognized by specific anti-rSm14 antibody raised in rabbits.

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Preliminary analysis of Sm14 in distinct fractions of Schistosoma mansoni adult worm extract

Agar-gel diffusion test (AGD), counterimmunoelectrophoresis (CIEP) and enzyme-linked immunosorbent assay(ELISA) were examined with the sera of skin test positives for paragonimiasis. The crude antigen(Paragonimus whole worm extracts: protein concentration, 7.56mg/ml) and human sera were used in AGD and CIEP. And in ELISA test, diluted antigen with 1:40,000 of crude antigen and diluted sera with 1:100, 1:200 were used in the test. The positive identical ratio between AGD and CIEP reactions is 98 % and negative identical ratio is 100 %. One or three precipitin bands are observed in AGD. One to seven precipitin bands are also revealed in CIEP. Especially, deeply stained bands are observed in CIEP than those of AGD. The positive identical ratios between AGD and ELISA tests are 96 % in 1:100 diluted sera, and 94 % in 1:200 diluted sera. But the negative identical ratios between AGD and ELISA tests are 97 % and 99 % respectively in 1:100 and 1:200 diluted sera. The positive identical ratios between CIEP and ELISA tests are 98 % and 96 % respectively in 1:100 and 1:200 diluted sera, but also 97 % and 99 % in 1:100 and 1:200. Control sera, such as clonorchiasis, amoebiasis and toxoplasmosis, revealed all negatives with Paragonimus antigen in AGD, CIEP and ELISA tests. By above results, ELISA was most sensitive, next CIEP and AGD. But AGD test appears to be more useful when used to crude antigen without cross reaction with other parasitic infections. CIEP test is basically equal in terms of precipitin reaction, but CIEP is able to be detected more sensitively and rapidly though less simple in handiwork than AGD. Consequently, three methods for immunological tests of paragonimiasis have good correlations with one another. Also, each of these has both merits and demerits in immunological test for paragonimiasis. But the ELISA test was proved to be the most sensitive and convenient tool for mass screening test, especially in case of using purified antigen.

http://parasitol.kr/upload/pdf/kjp-21-270.pdf

[Comparison Of Agar-Gel Diffusion Tests, Counterimmunoelectrophoresis And Enzyme-Linked Immunosorbent Assay In The Sera Of Skin Test Positives For Paragonimiasis]

Immunoprecipitins in human schistosomiasis detected with adult worm antigens released by 3M KC1.

Solubilization of Schistosoma mansoni antigens was obtained by agitation of adult worms in a 3M KCl solution. The protein contents of the KCl extrats varied from 0.35 to 0.96 mg/ml. Sera from 97 patients with hepatointestinal shistosomiasis and viable eggs in stools from a Brazilian endemic area were studied by immunoelectroomophoresis and Ouchterlony immunodiffusion methods with the KCl extract and with another antigen, obtained by homogenization of adult schistosomes in saline. The rate of positiveness of immunoprecipitation deterctions by immunoelectroomophoresis with the KCl extract was 53.5%. A correlation was verified between methods of detection and extration procedures, resulting in a better association of the extract obtained by agitation in 3M KCl and immunoelectroomophoresis.

https://www.arca.fiocruz.br/bitstream/icict/42069/2/MirianTendler_MauroScapin_IOC_1981.pdf

Schistosoma mansoni antigenic extracts obtained by different extraction procedures

Immunoelectroosmophoresis as a Rapid Method for Detecting Soluble Antigenic Fraction of Schistosoma mansoni

Fracao antigenica de Schistosoma mansoni obtida a partir de vermes adultos, precipitou em 35 minutos com soros de doentes com esquistossomose manonica e tornou-se visivel sem coloracao, utilizando-se o metodo de imunoeletroosmoforese (I.E.O.F.).

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Método rápido para detecção de fração antigênica de vermes adultos de Schistosoma mansoni

Utilizando 5 partidas de S. mamsoni adultos, obtidos pela infeccao de cobaios e camundongos, obtiveram-se tres extratos antigenicos (E1, E2 e E3). Estes extratos, em contacto com soro de doentes esquistossomoticos, forneceram as linhas de precipitacao da Fig. 1 pelo processo de imunoeletroosmoforese.

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Mauro Scapin

Papers

Schistosoma mansoni antigenic extracts obtained by different extraction procedures

Immunoelectroosmophoresis as a Rapid Method for Detecting Soluble Antigenic Fraction of Schistosoma mansoni

Immunoprecipitins in human schistosomiasis detected with adult worm antigens released by 3M KC1.

Método rápido para detecção de fração antigênica de vermes adultos de Schistosoma mansoni

Extração de frações antigênicas de S. Mansoni com KC1