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Schistosomiasis
Published in F. Y. Liew, Vaccination Strategies of Tropical Diseases, 2017
Graham F. Mitchell, Mark V. Rogers, Wilfred U. Tiu
The antidisease approach takes two forms, namely the induction of a disease-inhibiting immune response that acts against the egg and immunopathology. This whole approach to a schistosomiasis vaccine became a possibility with the demonstration that egg-induced pathology has an immunological basis and that the severity of immunopathologic responses was reduced in long-term infected individuals or in mice sensitized against egg antigens by multiple injections.12 Antiegg responses that may inhibit disease include those that inhibit egg production by female schistosomes (antifecundity immunity), that inhibit the maturation of eggs (antiembryonation immunity), that destroy the miracidium inside the egg (antimi- racidial immunity), or that in some other way inhibit production of immunopathologic antigens from the mature egg entrapped in tissues. One positive effect of granuloma formation is sequestration of hepatotoxins at least in mice with high S. mansoni worm burdens.25 Antiegg responses are also likely to have effects on transmission through a reduction in environmental contamination with eggs. Antiimmunopathology responses that may inhibit disease include all those postulated to inhibit either directly or indirectly the induction or expression of TH cell-dependent granulomatous inflammation. It is important to stress that the track record of immunologists in inhibiting specific immune responses at will — the negative vaccine or desensitization approach — is not good. Moreover, the antiimmunopathology effort has stalled somewhat, in parallel with uncertainties amongst cellular immunologists about much of the I-J+ suppressor T cell concept. Clearly, more information is required on cellular (e.g., Th1 vs. Th2 cells) and molecular events (e.g., cytokines) in immunoregulation before the idea of an antiimmunopathology vaccine becomes remotely attractive as a means of reducing the impact of schistosomiasis in communities.
Advances in engineering and delivery strategies for cytokine immunotherapy
Published in Expert Opinion on Drug Delivery, 2023
Margaret Bohmer, Yonger Xue, Katarina Jankovic, Yizhou Dong
One of the earliest studies examining gels for cytokine delivery, published in 2003, integrated IL-12 into a gelatin hydrogel and administered it to mice with transplanted colon carcinoma tumors [159]. When compared to systemic IL-12 injection, the hydrogel formulation resulted in greater tumor size reduction. In another study, IL-12 was loaded into an F2 gel matrix (made of polysaccharide polymer poly-N-acetyl glucosamine) as an adjuvant to SIINFEKL T-cell cancer vaccination [160]. A later study found that F2/IL-12 outperformed systemic IL-12 as an adjuvant for a schistosomiasis vaccine (soluble worm antigen preparation) in mice [161]. In addition to IL-12 delivery, gels have been studied for delivering GM-CSF. For example, a chitosan (CH)-based hydrogel containing GM-CSF and a chemotherapy drug (doxorubicin, cisplatin, or cyclophosphamide) was evaluated in mice against TC-1 cervical cancer cells [162]. Formulations containing all three components (CH, GM-CSF, chemotherapy) demonstrated stronger antitumor properties than CH+GM-CSF or CH+chemotherapy formulations by activating a tumor antigen (HPV-16 E7)-specific CD8+ T-cell response.
Overcoming challenges in the diagnosis and treatment of parasitic infectious diseases in migrants
Published in Expert Review of Anti-infective Therapy, 2020
Francesca F. Norman, Belen Comeche, Sandra Chamorro, Rogelio López-Vélez
Some progress has been made in the diagnosis of schistosomiasis in risk populations such as migrants, and some international guidelines currently consider screening for this infection in specific groups. To improve the treatment of schistosomiasis other therapeutic options such as mefloquine and combinations with artesunate have been studied recently in clinical trials in endemic areas [152,153]. A vaccine is under development (the anti-Schistosomiasis Vaccine Sm14 against S. mansoni and S. haematobium), and currently undergoing phase 2b testing in Senegal [154]. Diagnostic and therapeutic innovations for schistosomiasis appear to be gradually proving their usefulness and applicability in migrants in non-endemic areas and future progress in this area may be promising.
Ethical and practical considerations arising from community consultation on implementing controlled human infection studies using Schistosoma mansoni in Uganda
Published in Global Bioethics, 2022
Moses Egesa, Agnes Ssali, Edward Tumwesige, Moses Kizza, Emmanuella Driciru, Fiona Luboga, Meta Roestenberg, Janet Seeley, Alison M. Elliott
This paper presents a process of engaging communities in preparation for research towards a schistosomiasis vaccine trial using the controlled human infection model. This was undertaken to address the key ethical requirement of ensuring that the informed consent process is effective for all future volunteers. The process involved two phases of engaging the community; the first phase involved consulting on consenting materials and the second phase involved group sessions and key informant interviews.