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 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.

<p>Current Understanding of Immunity Against Schistosomiasis: Impact on Vaccine and Drug Development</p>

“…31,32 Based on the success of RA cercariae vaccination, several candidate antigens were identified based on reactivity of cells and sera from immunized mice. The results from testing these candidate antigens were less promising but provided the premise for two vaccine candidates: recombinant 28-kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) [33][34][35] and 14-kDa fatty acid-binding protein from Schistosoma mansoni (Sm14), [36][37][38][39][40] which have successfully completed phase III and phase IIa trials, respectively. The development of other candidate antigens has focused primarily on identifying key molecules that play crucial roles in parasite survival, such as membrane biogenesis/renewal, nutrient uptake and immune evasion strategies.…”

Schistosomiasis Elimination: Beginning of the End or a Continued March on a Trodden Path

“…One of these is the Sm14/GLA-SE schistosomiasis vaccine, primarily developed against S. mansoni , but which cross-reacts with S. haematobium and S. japonicum , has successfully completed Phase I and Phase IIa clinical trials, with Phase II/III trials underway in Senegal and further trials planned for Brazil. The paper by Tendler et al [33] in this special issue reviews the development of this vaccine candidate based on the fatty acid-binding protein (FABP) and formulated with the glucopyranosyl lipid A (GLA-SE) adjuvant. The paper follows the development of this product from the initial experiments delivering strongly supportive data to the ongoing Phase II studies.…”

Schistosoma mansoni egg-derived extracellular vesicles: A promising vaccine candidate against murine schistosomiasis

“…Multivalent vaccine formulation containing promising antigens have shown promising results as they might enhance subunit vaccine efficacy [8]. Out of many studied vaccine candidates, only three Schistosoma antigens have reached clinical trials; fatty acid-binding protein of 14 kDa from S. mansoni [9], glutathione-S-transferase of 28 kDa from S. haematobium [10] and S. mansoni tetraspanin-2 (TSP-2) of 23 KDa [11]. Studies on anti-schistosome vaccine are still on going.…”