Editorial: The Schistosomiasis Vaccine – It is Time to Stand up

Schistosomiasis is a severe parasitic disease, endemic in 74 developing countries with up to 600 million people infected and 800 million, mostly children, at risk of contracting the disease following infection predominantly with Schistosoma mansoni, Schistosoma haematobium, or Schistosoma japonicum. The disease burden is estimated to exceed 70 million disability-adjusted life-years, and leads to remarkably high YLD (years lived with disability) rates. Even more importantly, people with schistosomiasis are highly susceptible to malaria, tuberculosis, and hepatic and acquired immunodeficiency viruses. There is only one drug, praziquantel, currently available for treatment and it has high efficacy, low cost, and limited side effects. However, only 13% of the target population has received the drug, and those treated are at continuous risk of reinfection necessitating repeated drug administration and the emergence of drug-resistant parasites is a constant threat (1). Currently there is no vaccine. The a priori requirements for discovery of a vaccine formulation include the following: identification of protective key immune players in humans; characterization and isolation of target antigens; establishment of efficacy in terms of reduction of parasite burden as well as amelioration of immunopathology; establishment of safety; and finally, provision of considerable funds along with physical infrastructure and qualified personnel to carry out clinical trials. The target of >40% protection has been achieved with some schistosome molecules such as fatty acid binding protein (Sm14), paramyosin, calpain large subunit (Sm80), superoxide dismutase (SOD), glutathione S-transferase (GST), glyceraldehyde 3-phosphate dehydrogenase, and cysteine peptidases (2). Furthermore, Pearson et al. (3) identified the antigens selectively recognized by serum IgG1 and IgE of S. haematobium patients who acquired praziquantel-induced resistance (DIR) to the infection, or self-cured macaques following S. japonicum infection. The probed antigens were derived from S.mansoni and S. japonicum, likely because of the documented antigen conservation among the three main clinically important species, and were selected among those known to be secreted or localized to the tegument. The tegument is at the host–parasite interface, but its access by host effector antibodies is entirely prevented in healthy schistosomes, otherwise they would not survive a day, not to mention decades, in the host bloodstream. Anyhow, the study identified once again calpain, SOD, and GST as vaccine candidates together with surface membrane-associated antigens such as tetraspanins and glucose transporters, as well as an array of newly discovered target antigens. A remarkable finding in the study was the implication that type 2 (IgG1 and IgE) and not type 1-related antibodies are critical for human resistance against S. haematobium reinfection. Besides the worm tegument, which may not be accessed by host effector antibodies, the digestive tract is the other major interface between host and parasite. Schistosome peptidases responsible for digesting blood-born cells, components, and nutrients may be targeted, and possibly neutralized and blocked, by host antibodies and, thus, represent potential vaccine candidates. The timely study of Figueiredo et al. (4) reviewed what is known about the properties and vaccine potential of proteins secreted by the esophagus, and the lining (gastrodermis) of the blind-ended gut, namely Sm14, Sm10.3, venom allergen-like (VAL) protein, Cu–Zn SOD, cathepsin B, and cathepsin L.