Why the radiation-attenuated cercarial immunization studies failed to guide the road for an effective schistosomiasis vaccine: A review

Abstract

Graphical abstractSchistosomula- and adult worms-derived antigens induce predominant Th1 immune responses. The radiation-attenuated cercariae vaccine efficacy is dependent on induction of Th1 and Th2 immune responses. Accordingly, schistosomula- and adult worms-derived antigens used for effective vaccination must be combined with Th2 immune responses-inducing cytokines or molecules as adjuvant.

Induction of Protective Immune Responses Against Schistosomiasis haematobium in Hamsters and Mice Using Cysteine Peptidase-Based Vaccine

“…mansoni consistently, and reproducibly elicited highly significant ( P < 0.0001) reduction in worm burden of 70% ±3. The reduction was also highly significant for decrease in worm liver ( P < 0.0001) and small intestine ( P < 0.001) egg counts but only of approximately 50% ( 14 ).…”

“…This belief was based on preponderance of interferon-gamma (IFN-γ) released by bronchoalveolar leukocytes, total lung tissue, and lung-draining lymph nodes in radiation-attenuated (RA) cercariae-vaccinated mice ( 11 , 12 ). Lung schistosomula-derived antigens seeping in lung tissues or released from extravasated dying larvae expectedly induce preponderant type 1 immune responses [( 13 , 14 ) and references therein]. Yet, these immune responses might be irrelevant to parasite attrition, as it must be reiterated healthy schistosomes are exclusively intravascular and may not be directly affected by the immune events in lung alveoli, parenchyma, or draining lymph nodes.…”

“…We have well-learned the lessons of the successful RA vaccine model and thought it is imperative to use type 2-, not type 1-inducing cytokines or molecules as adjuvants to the schistosome-derived antigens used for vaccination ( 14 ). The highly significant ( P < 0.0001) and reproducible protection against challenge S. mansoni worms achieved in mice, immunized with larval antigens derived from excretory–secretory products (ESP), namely recombinant glyceraldehyde 3-phosphate dehydrogenase (rSG3PDH) and 2-cys peroxiredoxin-derived peptide in a multiple antigen peptide construct (PRX MAP) in conjunction with papain, interleukin (IL)-25, IL-33, or thymic stromal lymphopoietin (TSLP), supported our belief.…”

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

“…Since currently available vaccine candidate formulations mediate type 1-biased protective immunity, which is limited or partial at best, it is important to revisit the lessons of the radiation-attenuated (RA) cercarial vaccine ( 9 ). In this respect, a meta-analysis of the experimental studies undertaken with the RA cercarial vaccine in mice (755 observations from a total of 105 articles) was performed by Fukushige et al ( 10 ), who reported that the RA vaccine has the potential to induce protection as high as 78% with a single dose of vaccine.…”

“…(3) Specific antibodies may access the worm gut lumen and those that escape immediate digestion might be able to neutralize and interfere with enzymes critical for worm feeding and fecundity, but not survival, as these processes by definition impact on juvenile and adult worms not schistosomula migrating in the lung capillaries and liver sinusoids ( 4 ). (4) We are left then with the hunt and chase theory, whereby immune antibodies and cells interact with excreted–secreted parasite products in the vicinity of migrating schistosomula, alarming and activating effector immune cells ( 2 , 9 , 12 ). (5) Eosinophils and basophils would be particularly effective immune cells but need a type 2 immune environment for recruitment and activation ( 2 , 9 , 12 , 13 ).…”