Safety and immunogenicity of the Sm-p80 GLA-SE schistosomiasis vaccine – Nature

Report on the Phase 1 Clinical Trial of the SchistoShield® Vaccine for Schistosomiasis

Executive Summary

This report details the outcomes of a Phase 1, first-in-human clinical trial of the SchistoShield® vaccine, designed to combat schistosomiasis. Schistosomiasis is a neglected tropical disease intrinsically linked to poverty, representing a significant obstacle to achieving Sustainable Development Goal 1 (No Poverty) and Sustainable Development Goal 3 (Good Health and Well-being). The development of an effective vaccine is a critical strategy for meeting SDG Target 3.3, which aims to end the epidemics of neglected tropical diseases by 2030. The trial successfully evaluated the vaccine’s safety and immunogenicity, demonstrating that it was well-tolerated and capable of inducing robust immune responses. These positive results support the vaccine’s advancement to further trials in endemic regions, marking a crucial step towards reducing global health inequalities and achieving universal health coverage.

1.0 Introduction: Aligning with Sustainable Development Goals

Schistosomiasis, a poverty-related neglected tropical disease, affects hundreds of millions of people, primarily in sub-Saharan Africa, undermining health and economic stability. The World Health Organization’s roadmap for 2021–2030 targets the elimination of schistosomiasis, a goal that aligns directly with the United Nations’ Sustainable Development Goals. Current control methods, reliant on chemotherapy, are hampered by high rates of reinfection. The development of a safe, effective, and long-lasting vaccine is therefore a global public health priority.

The SchistoShield® vaccine represents a significant contribution to this effort. By targeting the Sm-p80 antigen of the Schistosoma mansoni parasite, it aims to provide comprehensive protection. Preclinical studies have shown its potential to not only prevent infection but also reduce pathology and block transmission, thereby contributing to several key SDGs:

• SDG 3 (Good Health and Well-being): Directly addresses the goal of ending the epidemic of a major neglected tropical disease.
• SDG 1 (No Poverty): Aims to break the cycle of disease and poverty that schistosomiasis perpetuates in vulnerable communities.
• SDG 10 (Reduced Inequalities): Focuses on a disease that disproportionately affects the world’s poorest populations.

This Phase 1 trial was initiated to establish the foundational safety and immunogenicity data required to advance this promising candidate into populations most affected by the disease.

2.0 Methodology of the Clinical Trial

The study was a Phase 1, first-in-human, open-label, dose-escalation trial conducted with healthy adults in the United States. This methodical approach reflects a commitment to SDG 9 (Industry, Innovation, and Infrastructure) by building the necessary scientific evidence for a novel health technology.

2.1 Trial Design and Participants

A total of 45 healthy adults, aged 19 to 55, were enrolled and sequentially assigned to one of five study groups. The trial was designed to assess different dosages of the Sm-p80 antigen, the impact of the GLA-SE adjuvant, and varying vaccination schedules.

1. Group A: 100 µg Sm-p80 antigen without adjuvant (unadjuvanted comparator).
2. Group B: 10 µg Sm-p80 antigen with 5 µg GLA-SE adjuvant.
3. Group C: 30 µg Sm-p80 antigen with 5 µg GLA-SE adjuvant (delayed booster schedule).
4. Group D: 30 µg Sm-p80 antigen with 5 µg GLA-SE adjuvant (standard schedule).
5. Group E: 100 µg Sm-p80 antigen with 5 µg GLA-SE adjuvant.

Participants in Groups A, B, D, and E received a three-dose series on Days 1, 29, and 57. Group C received doses on Days 1, 29, and 180 to evaluate a delayed booster effect.

2.2 Endpoints and Analysis

The primary objectives were to evaluate the safety, reactogenicity, and immunogenicity of the vaccine formulations. Safety was monitored through the assessment of solicited and unsolicited adverse events (AEs). Immunogenicity was measured by quantifying anti-Sm-p80 IgG antibody levels in serum samples via ELISA.

3.0 Key Findings and Results

The trial results provide strong support for the continued development of the SchistoShield® vaccine as a tool for achieving global health equity under the SDGs.

3.1 Safety and Tolerability Profile

The vaccine was well-tolerated across all study groups. Key safety findings include:

• No serious adverse events (SAEs), medically-attended adverse events (MAAEs), or deaths were reported.
• The majority of solicited local and systemic AEs were mild to moderate in severity.
• The most common solicited systemic AEs were fatigue (69%) and headache (58%).
• The most common local AEs were tenderness (96%) and pain (65%) at the injection site.
• Fever was reported by only one participant.

This acceptable safety profile is a critical prerequisite for deploying a new health intervention in vulnerable populations, ensuring that the pursuit of SDG 3 does not cause undue harm.

3.2 Immunogenicity Response

All vaccine formulations successfully induced an immune response, with the adjuvanted formulations demonstrating superior performance. This outcome is a promising indicator of the vaccine’s potential to contribute to the eradication goals of SDG Target 3.3.

• All formulations induced a significant increase in anti-Sm-p80 IgG geometric mean titers (GMTs) compared to baseline, particularly after the second dose.
• Responses were consistently and significantly higher in the adjuvanted groups (B, C, D, and E) compared to the unadjuvanted group (A).
• Among the groups on the standard schedule, GMTs were comparable across the different antigen dosages (10, 30, and 100 µg), suggesting no clear dose-response relationship in this small cohort.
• The delayed booster schedule (Group C) induced the highest nominal peak response 28 days after the third dose.
• Antibody levels remained significantly above baseline at the final follow-up time point in all groups.

4.0 Discussion and Future Directives

The findings from this Phase 1 trial are a significant milestone in the fight against schistosomiasis. The demonstration of an acceptable safety profile and robust immunogenicity in a non-endemic population provides the necessary foundation for progressing the SchistoShield® vaccine to the next stage of clinical development.

The successful completion of this trial has enabled the initiation of a Phase 1b trial in endemic areas of Africa (Madagascar and Burkina Faso). This crucial step directly addresses SDG 10 (Reduced Inequalities) by ensuring that research and development efforts are centered on the populations most burdened by the disease. The collaborative effort involving academic institutions, private industry (PAI Life Sciences Inc.), and government bodies (NIAID) exemplifies the multi-stakeholder partnerships essential for achieving the SDGs, as outlined in SDG 17 (Partnerships for the Goals).

Further development, including planned Phase 2 trials and the establishment of a functional assay to serve as a surrogate of protection, will continue to advance this vaccine candidate. The continued progress of the Sm-p80 vaccine holds the potential to become a transformative tool in public health, contributing significantly to the global goal of eliminating schistosomiasis and creating a healthier, more equitable world.

Analysis of Sustainable Development Goals in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

The article on the SchistoShield® vaccine trial for schistosomiasis addresses several Sustainable Development Goals (SDGs) due to its focus on health, poverty, and scientific innovation.

• SDG 3: Good Health and Well-being

  This is the most direct and prominent SDG addressed. The entire article focuses on the development of a vaccine to combat schistosomiasis, a “neglected tropical disease” that poses a significant public health threat. The research aims to create an “efficacious and safe vaccine” to prevent infection, reduce disease pathology, and ultimately improve the health outcomes for hundreds of millions of people at risk.

• SDG 1: No Poverty

  The article explicitly states that “Schistosomiasis is a poverty-related neglected tropical disease.” Diseases like schistosomiasis disproportionately affect poor populations, creating a cycle of poverty and ill-health by reducing productivity and increasing healthcare costs. Developing a vaccine is a crucial intervention that can help alleviate this burden, contributing to poverty reduction in endemic areas.

• SDG 9: Industry, Innovation, and Infrastructure

  The article details a “Phase 1 first-in-human, dose-escalation trial,” which represents the cutting edge of scientific research and innovation in the biotechnology and pharmaceutical sectors. The development of the vaccine itself, which combines a specific antigen (Sm-p80) with an adjuvant (GLA-SE), and the creation of new functional assays to measure its effectiveness, are prime examples of enhancing scientific research and technological capabilities to solve global challenges.

• SDG 17: Partnerships for the Goals

  The vaccine trial is a collaborative effort involving multiple institutions, including research institutes (Kaiser Permanente Washington Health Research Institute, Seattle Children’s Research Institute), government bodies (National Institute of Allergy and Infectious Diseases – NIAID), and private companies (PAI Life Sciences Inc). Furthermore, the article mentions the trial is expanding from the United States to “endemic areas of Africa (Madagascar and Burkina Faso)” as well as other international sites (The Netherlands and Uganda), highlighting a global partnership to advance science and public health.

2. What specific targets under those SDGs can be identified based on the article’s content?

Based on the article’s focus, several specific SDG targets can be identified:

1. Target 3.3: End epidemics of neglected tropical diseases

   The article is centered on schistosomiasis, which it identifies as a “neglected tropical disease.” The ultimate goal of developing an “efficacious vaccine with long-lasting protection” is to control and eliminate this disease. The text directly references the “World Health Organization launched a neglected tropical diseases Road Map for 2021–2030 that targets the elimination of schistosomiasis,” aligning the research perfectly with this target.

2. Target 3.b: Support the research and development of vaccines and medicines

   This target calls for supporting R&D for diseases that primarily affect developing countries. The article is a detailed report on the clinical trial of a vaccine for schistosomiasis, a disease with the “greatest burden in sub-Saharan Africa.” The entire study, from preclinical animal models to the first-in-human trial and its expansion to endemic areas in Africa, exemplifies the R&D process that this target aims to promote.

3. Target 9.5: Enhance scientific research and encourage innovation

   The clinical trial described is a sophisticated scientific endeavor. It involves dose-escalation studies, the use of a novel adjuvant (GLA-SE), and advanced immunogenicity assays. The discussion about developing “a functional enzymatic assay as potential readout for a clinical trial” to serve as a “vaccine surrogate of protection” is a clear example of enhancing scientific research and innovation to overcome challenges in vaccine development.

4. Target 17.6: Enhance North-South, South-South and triangular regional and international cooperation on and access to science, technology and innovation

   The project’s structure reflects this target. The initial Phase 1 trial was conducted in the United States, a developed nation. The article states that this work “supported the initiation in 2023 of a larger Phase 1b trial among schistosome-endemic populations in Africa (Madagascar and Burkina Faso).” This progression represents a clear North-South collaboration to transfer and apply scientific research where it is most needed.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

Yes, the article mentions and implies several quantitative and qualitative indicators that can be used to measure progress.

• Indicators for Target 3.3 (End NTDs)

  • Number of people requiring interventions against NTDs (Indicator 3.3.5): The article states that schistosomiasis impacts “more than 700 million people who live in endemic areas and are at risk of infection.” The success of the vaccine would be measured by a reduction in this number.
  • Vaccine Efficacy Metrics (Implied): The article mentions that in nonhuman primate studies, the vaccine was effective in “killing pathogenic female worms and reducing host organ pathology and egg excretion.” These are specific, measurable health outcomes that would serve as indicators of the vaccine’s impact on the disease burden.
  • Reduction in Reinfection Rates (Implied): The article notes that current chemotherapy is compromised by “reinfection requiring regular re-treatment.” A successful vaccine offering “long-lasting protection” would be measured by a significant decrease in reinfection rates in vaccinated populations.

• Indicators for Target 3.b (Support R&D)

  • Clinical Trial Progression (Implied): The advancement of the SchistoShield® vaccine from preclinical studies to a “Phase 1 first-in-human” trial and now to a “Phase 1b trial” and a planned “Phase 2 trial” is a direct indicator of progress in the R&D pipeline for NTD vaccines.
  • Immunogenicity and Safety Data (Mentioned): The article provides detailed data on the vaccine’s safety (“solicited AEs,” “unsolicited AEs”) and its ability to induce an immune response (“anti-Sm-p80 IgG ELISA responses,” “geometric mean titers”). These data points are critical indicators of a vaccine candidate’s viability.

• Indicators for Target 9.5 (Enhance Scientific Research)

  • Development of Novel Research Tools (Mentioned): The article discusses progress in developing a “reproducible, quantitative, and functional assay” to measure how antibodies inhibit the Sm-p80 enzyme. The creation and validation of such an assay is an indicator of enhanced research capability and innovation.
  • Number of Vaccine Candidates in Development (Mentioned): The article notes that “multiple human vaccine candidates targeting different schistosome antigens are in clinical trials,” including SchistoShield® and the “recombinant S. mansoni Tetraspanin-2 Alhydrogel vaccine.” This number serves as an indicator of the overall research effort in the field.

4. Table of SDGs, Targets, and Indicators

Source: nature.com