Abstract
Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.
Highlights
Schistosomiasis is a poverty associated chronic disease caused by parasitic trematodes of the genus Schistosoma [1]
The HIV-adenovirus-vectored (Ad26.EnvA.01 and Ad35-EnvA) candidate vaccines induced better efficacy and greater T cell responses in an American cohort compared to South and East African subjects [58]. These findings suggest that the baseline immune profile of African populations may interfere with adequate vaccine responses and this effect is especially important for the viral vectored and live vaccines such as the MVA85A and Ad26/35-EnvA, and Bacillus Calmette-Guérin (BCG) and YF-17D, respectively [55, 57, 61]
In this review we focus on the concomitant parasitic and viral (Cytomegalovirus) infections which are highly prevalent among schistosomiasis endemic populations in the low and middle income countries (LMIC) [73, 74]
Summary
Schistosomiasis is a poverty associated chronic disease caused by parasitic trematodes of the genus Schistosoma [1]. The full dependency on a single drug poses a threat of drug resistance [7] This leaves vaccination a key approach for the control and possible elimination of schistosomiasis. The current overall consensus on preferred product characteristics (PPC) for an effective prophylactic vaccine is induction of 75% reduction in worm burden in immunized individuals and egg excretion in infected patients [9]. There is inadequate understanding of how past and existing schistosome infections, repeated exposure, poly-parasitism and prior treatment explicitly structure the immune system in individuals, within and between the different populations. These factors are likely to increase heterogeneity in vaccine responses. We review the immunological challenges for schistosome vaccine development and testing in endemic settings and provide perspectives of how this scientific priority area can be accelerated
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