Vaccine value profile for schistosomiasis

The development of this Vaccine Value Profile has been commissioned by WHO’s Immunization, Vaccines and Biologicals (IVB) department on the recommendation of IVB’s Product Development for Vaccines Advisory Committee, to Duke University. 

This ‘Vaccine Value Profile’ (VVP) for schistosomiasis is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic, and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public private partnerships, and multi-lateral organizations. All contributors have extensive expertise on various elements of the schistosomiasis VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Summary

The global public health need for a schistosomiasis vaccine is based on (a) the morbidity, mortality, and gender-based and socioeconomic implications of the illness, and (b) the global ambition to eliminate the disease (not just achieve its control).

Even with MDA, WASH, snail control, and other interventions, there is still a large burden of schistosomiasis. The Global Burden of Disease 2019 study found that schistosomiasis was responsible for 1.64 million DALYs. About 236.6 million people required treatment for schistosomiasis in 2019. Poor and rural communities are disproportionately affected. The risk is greatest in areas with poor access to safe water and adequate sanitation; high-risk activities include farming irrigated fields, fishing, washing cars, and washing clothes in infected water sources. Out-of-pocket costs associated with schistosomiasis have been poorly studied, but are likely to be considerable for severe disease. Cost of illness studies estimate that over 95% of total costs associated with schistosomiasis are due to productivity losses (e.g., lost wages due to illness and death). There are also productivity costs associated with livestock schistosomiasis. Schistosomiasis has multiple gendered dimensions—for example, FGS is a stigmatizing condition that affects reproductive health.

WHO launched a NTD Road Map for 2021–2030 that targets the elimination of schistosomiasis as a public health problem in all endemic countries. Under “actions required,” the Road Map states: “consider development of a vaccine for humans and animals to prevent reinfection and reduce transmission.” In addition to political and policy support for vaccine development, other supportive policy actors include the US NIH, the US Department of Defense, the Bill & Melinda Gates Foundation, the European Community, FIOCRUZ and the Brazilian Government, Australia’s NHMRC, SCI, and IVI.

Preferred product characteristics for a schistosomiasis vaccine, agnostic to a specific candidate, include: prevention of infection by one of the three human Schistosoma parasites (S. mansoni, S. haematobium, or S. japonicum); targets populations in endemic countries or regions, especially adults (18–59 years of age) in high-risk occupations or areas and high-risk school-age children (3–12 years of age); 2-dose, parenteral administration; at least 2–3 years of protection after last dosing; good safety profile; can be co-administered with praziquantel MDA and other interventions; storage at from −20 ◦C to 4◦C; and stability expected to be over 3 years.

There are currently four vaccine candidates in clinical trials, described in detail in this paper:

1. Bilhvax (Sh28GST vaccine), which has undergone phase 1–3 trials.
2. The Sm-14 Humanitarian Schistosomiasis Vaccine Initiative, which has undergone Phase 1a and 1b in a non-endemic area of Brazil between 2010 and 2015; 2a and 2b trials in a Senegalese area endemic for both S. mansoni and S. haematobium conducted by EPLS between 2015 and 2019; followed by a Phase 2c trial which began in 2020 and is expected to reach conclusion in an endemic area in Senegal by the end of 2023. Safety was already attested.
3. The Human Schistosomiasis Vaccine, which has undergone Phase 1 trials; a Phase 1/2 proof-of-efficacy trial in healthy exposed adults is currently underway in Uganda.
4. SchistoShield®: A Phase 1a clinical trial has been completed in infection naïve adults in the US. No significant safety concerns have been observed in all of the groups including with dose escalation. Vaccine appears to be well tolerated and elicits pronounced vaccine-mediated responses. Phase 1b/2A dose-escalation trial among African adults, with a planned future age de-escalation study in school-aged children (Burkina Faso, Madagascar) is currently underway.

Several modelling studies have explored the use of a schistosomiasis vaccine and quantified its potential impact on disease burden and/or transmission. Key findings are: (i) vaccination used in combination with MDA would tend to provide greater benefits (e.g., the combination would reduce transmission more quickly) than using either alone; (ii) interrupting transmission should be more readily achieved in low transmission settings compared to moderate and high transmission settings; (iii) the duration of protection seems to be the largest driver of vaccination’s impact; (iv) mass vaccination of the community would more quickly interrupt transmission and has the greatest chances of achieving the WHO goals compared to vaccinating other target populations; and (v) vaccinating school-aged children seems to be the next best strategy, followed by infant vaccination (it would take several years to interrupt transmission in a community when only vaccinating infants as there is not a reduction in the current burden in the population when using this strategy).

Modelling studies have also estimated the socioeconomic impacts of a schistosomiasis vaccine. These have shown that a vaccine of at least 90% efficacy would be cost-effective and, in some circumstances, could generate cost savings, compared to MDA from the healthcare provider perspective. Vaccination would be more cost-effective than MDA, when the vaccine cost up to $9.20. However, this threshold cost varied by study and transmission setting (e.g., higher costing vaccines remained cost-effective in higher transmission settings) and ranged from $3 to $9.20. The duration of protection offered by a vaccine is a large driver of its cost-effectiveness and is a driver of which target population it is most cost-effective to vaccinate (e.g., with a shorter duration of protection it is more cost-effective to vaccinate school-aged children). Vaccination would be more cost-effective in higher transmission settings compared to lower transmission settings.

Finally, there is high overall feasibility when it comes to implementing schistosomiasis vaccines. First, they could be implemented within existing delivery systems and vaccines in current development have relatively simple dosing schedules. They could be co-administered with routine measles or preschool vaccines, alongside MDA programs, and with HPV vaccines. Schistosomiasis vaccines have moderate to high commercial attractiveness, since there is significant potential LMIC vaccine demand, many endemic countries are eligible for Gavi support (interest from Gavi has not been confirmed, but schistosomiasis vaccines are expected to fall within their remit), and there is also some HIC utility for military populations. Uptake is expected to be high, given the existing level of acceptance of vaccination, mass drug administration, and other health care approaches. Nevertheless, we note that Gavi’s procurement decisions are based primarily on deaths avoided, and the comparatively low mortality may not make this an attractive investment. The societal costs of morbidity need to be better enumerated to strengthen the case for donor funding of schistosomiasis vaccines (including in comparison to funding treatment). As we noted in the introduction, schistosomiasis vaccines also fit well with the One Health concept synergizing human and animal health: there are opportunities for using veterinary vaccines in the control of human schistosomiasis.