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

Abstract

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequalities, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although schistosomiasis control approach has shown that chemotherapy is capable of reducing morbidity in humans, rapid re-infection is a reminder that the impact of drug treatment on transmission control or elimination initiatives is marginal. In addition, and regardless of 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 and to be followed in Brazil. Discovery and experimental phases were long term achievements leading to a robust collection of data that are strongly supporting the presently ongoing Clinical Phase. This paper reviews the development of the Sm14 vaccine formulated with GLA-SE (Glucopyranosyl Lipid A), from the earlier experimental developments to clinical trials including the recent status of Phase II studies.

A comprehensive and critical overview of schistosomiasis vaccine candidates

“…Accordingly, the results supported this product as a safe, strongly immunogenic vaccine against schistosomiasis, and paved the way for follow-up phase 2 trials (2015–2017). In phase 2a trial, rSm14 vaccine was safe with long lasting immunogenicity when administrated to 30 male adults from endemic area for both S. mansoni and S. haematobium in Senegal River Basin (Tendler et al 2018 ). Accordingly, Phase 2b and phase 3 trials are planned (McManus et al 2020 ).…”

Doenças infecciosas e parasitárias no contexto brasileiro

“…Segundo Tendler et al (2018), a vacina Sm14 com o adjuvante GLA-SE (glucopiranosil lipídio A em emulsão óleo/água), é a primeira vacina brasileira anti-helmintica a ir para estudos clínicos em humanos (TENDLER et al, 2018).…”

“…Em relação a imunização, obteve uma mistura de Th1/Th2, com aumento de IgG1 e IgG3 no primeiro mês, IgG2 e IgG4 a partir do segundo mês, além de citocinas (IL-2, IL-5, IL-10, IFN e TNF) e ausência de IgE (SANTINI-OLIVEIRA et al, 2015). Prosseguindo na avaliação de segurança e imunogenicidade, o estudo Ib envolveu 10 voluntários adultos do sexo feminino, de área não endêmica, que foi concluído com sucesso em 2012 (TENDLER et al, 2018).…”

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

“…A Phase 1b clinical study, evaluating the safety/immunogenicity of the Sm14/GLA-SE vaccine in healthy female volunteers, was concluded successfully in 2012 [ 76 ]. This paved the way for a Phase 2a clinical trial ( ) undertaken during 2015–2017 in male adults resident in an area in the Senegal River Basin highly endemic for both S. mansoni and S. haematobium ; the results of the trial confirmed the safety and long-lasting immunogenicity of the Sm14/GLA-SE vaccine [ 77 ]. A subsequent Phase 2b trial design and protocol were defined for infected Senegalese school children living in the same area endemic for both schistosome species and further Phase 2c and 2d (in Brazil) and Phase 3 (in Senegal) clinical trials with Sm14/GLA-SE are scheduled [ 77 ].…”