Developing a mathematical model for the evaluation of the potential impact of a partially efficacious vaccine on the transmission dynamics of Schistosoma mansoni in human communities

Stylianou, Andria; Hadjichrysanthou, Christoforos; Truscott, James E.; Anderson, Roy M.

doi:10.1186/s13071-017-2227-0

Cited by 25 publications

(32 citation statements)

References 32 publications

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“…The macroparasite transmission dynamics model for the transmission of the parasite to measure outcomes in human populations has predicted that an Sm-p80-based vaccine has the potential to contribute greatly to reducing the burden of schistosomiasis and parasite transmission in endemic regions. 10 Immunolocalization analyses of confocal images demonstrated that Sm-p80 protein is distributed in and on the surface epithelial syncytium of adult worms, with a 2.5-fold increased intensity (P < 0.001) in Sm-p80-specific fluorescence in female worms compared with male counterparts. Given that Sm-p80 is the vaccine antigen, we postu-late that the upregulation and increased accessibility of Sm-p80 renders female worms more susceptible than male worms to immune-mediated killing.…”

Section: Discussionmentioning

confidence: 94%

“…Using these data and incorporating inhibitory effects on parasite mortality, fecundity, and infection transmission, mathematical modeling was used to predict the overall potential efficacy of our vaccine on disease transmission dynamics. The macroparasite transmission dynamics model for the transmission of the parasite to measure outcomes in human populations has predicted that an Sm‐p80‐based vaccine has the potential to contribute greatly to reducing the burden of schistosomiasis and parasite transmission in endemic regions …”

Section: Discussionmentioning

confidence: 99%

“…8,9 Mathematical modeling evaluating the impact of a vaccine on transmission dynamics has suggested that a partially protective vaccine with an efficacy as low as 60% could prevent transmission in low-and moderately endemic areas. 10 Compartmental model simulation of schistosomiasis transmission in endemic regions has predicted that, compared with MDAonly programs, vaccination with a partially protective vaccine combined with MDA would be advantageous in reducing the acquisition of new worms and lowering egg release from residual worms in the environment. 11 To date, there are three schistosomiasis vaccine candidates in various phases of human clinical trials: S. haematobium glutathione S-transferase (Sh28GST), 12 S. mansoni tetraspanin, a 9-kDa surface antigen (Sm-TSP-2), 13 and S. mansoni 14-kDa fatty acid-binding protein (Sm14).…”

Section: Introductionmentioning

confidence: 99%

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Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Zhang

Molehin

Rojo

et al. 2018

Annals of the New York Academy of Sciences

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Schistosomiasis is of public health importance to an estimated one billion people in 79 countries. A vaccine is urgently needed. Here, we report the results of four independent, double-blind studies of an Sm-p80-based vaccine in baboons. The vaccine exhibited potent prophylactic efficacy against transmission of Schistosoma mansoni infection and was associated with significantly less egg-induced pathology, compared with unvaccinated control animals. Specifically, the vaccine resulted in a 93.45% reduction of pathology-producing female worms and significantly resolved the major clinical manifestations of hepatic/intestinal schistosomiasis by reducing the tissue egg-load by 89.95%. A 35-fold decrease in fecal egg excretion in vaccinated animals, combined with an 81.51% reduction in hatching of eggs into the snail-infective stage (miracidia), demonstrates the parasite transmission-blocking potential of the vaccine. Substantially higher Sm-p80 expression in female worms and Sm-p80-specific antibodies in vaccinated baboons appear to play an important role in vaccine-mediated protection. Preliminary analyses of RNA sequencing revealed distinct molecular signatures of vaccine-induced effects in baboon immune effector cells. This study provides comprehensive evidence for the effectiveness of an Sm-p80-based vaccine for schistosomiasis.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Zhang

Molehin

Rojo

et al. 2018

Annals of the New York Academy of Sciences

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“…Since their inception, substantial improvements in computational power have allowed the use of individual-based models to efficiently sample their resulting distributions over time and overcome the inherent noise in the dynamics. An alternative approach using deterministic compartment-based models, has been used to investigate the effects of vaccination, but this approach allows for less scope for including biological complexity [22, 23]. The transmission cycle, which is related to previously published models [11, 21, 24], is as follows:

Mature adult schistosomes reproduce within human hosts monogamously.

…”

Section: Methodsmentioning

confidence: 99%

“…of human hosts in population, N 1000Baseline prevalence in SACHigh-transmission setting, 65%; Moderate-transmission setting, 45% (Obtained by scaling the contact rate between human hosts and the reservoir)Age-dependent contact with reservoirAges 0–4: 0.032; 5–9: 0.162; 10–14: 1.0; 15+: 0.05[43]Shape parameter α of Gamma distributed risk factor0.24[43]Kato–Katz test aggregation parameter, k 0.87[44, 45]Exponential fecundity decay, z 0.0007/worm[23, 46]Maximum fecundity, λ0.14 egg counts/female worm[45, 47]Average worm life-span5.7 years[48]Human demographyBased on Kenya’s demographic profile[49] …”

Section: Methodsmentioning

confidence: 99%

Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

et al. 2019

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BackgroundSchistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective.MethodsUsing an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations.ResultsWe found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults.ConclusionsThe ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety and duration of protection, as well as the subset of population targeted for vaccination. However, our results indicate that if a vaccine could be developed with reasonable characteristics and for a sufficiently low cost, then vaccination programmes can be a highly cost-effective method of controlling schistosomiasis in high-transmission areas. The population-level immunity generated by vaccination will also inevitably improve the chances of interrupting transmission of the disease, which is the long-term epidemiological goal.

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The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis

Melo¹,

Mendes²,

Alves³

et al. 2019

Molecular Immunology

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Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria.The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107-121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107-121) significantly reduced worm burden (48-50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107-121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.

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Developing a mathematical model for the evaluation of the potential impact of a partially efficacious vaccine on the transmission dynamics of Schistosoma mansoni in human communities

Cited by 25 publications

References 32 publications

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison

The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis

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