Advancing Polio Eradication with Novel Oral Polio Vaccine type 2 (nOPV2)

Introduction:

The development of the novel oral polio vaccine type 2 (nOPV2) began in 2011, and after a decade of rigorous research and testing, it was rolled out for field use in March 2021 under an Emergency Use Listing (EUL). This innovative tool was designed to more sustainably curb the spread of type 2 circulating vaccine-derived poliovirus (cVDPV2) outbreaks. By February 2024, over 1 billion doses of nOPV2 had been administered across 35 countries. In December 2023, nOPV2 received WHO prequalification, becoming the first vaccine to successfully navigate the EUL pathway and setting a precedent for future drug innovations.

As the global rollout of nOPV2 continues, it is vital to recognize the decade of committed effort that went into its development and reflect on the valuable lessons learned throughout the process. These lessons can be categorized into three key areas: technology and development, global health, and organizational governance.

Key lessons learned, and current/future actions:

-Technology Development
Several key aspects of the technological development of nOPV2 offer valuable lessons for approaching other global health initiatives. These include:

• Foresight: Recognizing early on that circulating vaccine-derived poliovirus (cVDPV), which had been relatively minor during the early stages of polio eradication when wild poliovirus (WPV) cases dominated, would become a significant challenge in the final stages of eradication.
• Leveraging Innovations in Science: Building on scientific advances that revealed the genetic instability of the Sabin OPV strains—leading to reversion to polio-producing viruses—and exploring the potential for creating more stable OPV variants with enhanced genetic stability.
• Innovative Product Development: Drawing on global expertise in product development to create candidate nOPVs that were as attenuated as OPV type-2 strains, while demonstrating improved genetic stability, as well as comparable antigenicity and immunogenicity.
• Innovative Approaches to Clinical Trials: The use of containment strategies in Phase I trials and a complex, multidimensional study design that included new approaches to data collection and evaluation in later phases. Control-arm studies were conducted prior to the switch to ensure conformity with global containment requirements.
• Accelerated Product Approval for Public Health Value: The process of speeding up product approval through alignment with the newly created WHO Emergency Use Listing (EUL) process, which resulted in the first-ever EUL granted for a vaccine.
• Balancing Ethical and Financial Risks with Clinical Urgency: Taking calculated risks in response to the worsening cVDPV2 situation in 2019, which led to the decision to proceed with at-risk, large-scale production of nOPV2. This included an early investment model, with Indonesia’s PT Bio Farma contracted to produce up to 200 million doses by the end of 2020 and a minimum of 500 million doses per year thereafter, ensuring availability as soon as the EUL was granted.

-Global Health
The rollout of nOPV2 presents several key lessons that are relevant to the broader global health agenda, including:

• Adapting to the Disruptive Global Context: Effectively managing the impact of the COVID-19 crisis by securing alternative vaccine supplies and enhancing communication efforts was crucial in limiting the rise of cVDPV. Additionally, leveraging the lessons learned from the COVID-19 response played a pivotal role in the successful rollout of nOPV2.
• Building on an Established Platform and New Partnerships: The rollout provided an ideal opportunity to unite all relevant stakeholders around a common goal and high-priority issue, building on the strong foundation of polio eradication efforts while bringing in new partners.
• Extensive Consultative Processes with Country Stakeholders: Recognizing the diverse contexts and levels of risk across different countries, the approach was adapted to meet local needs. This included transparent sharing of evidence, targeted communications, and strong advocacy to ensure that global recommendations were tailored to local campaigns.
• Proactive and Effective Communication: Planning for product acceptance and uptake, addressing misinformation, and utilizing digital platforms for social mobilization to raise awareness and build confidence in the vaccine were key at multiple stages of development and rollout.
• Forecasting Supply Needs: Effective coordination through multi-channel communication with countries, flexible procurement models, and adaptive manufacturing processes was essential in addressing the challenges presented by the COVID-19 context and ensuring that supply needs were met.
• Prioritizing Informed Decision-Making at the Country Level: Ensuring the availability of materials in multiple languages to support decision-making, foster stakeholder buy-in, and enable better verification processes was critical for successful implementation at the national level.

-Organization & Governance
The organizational and governance lessons learned from nOPV2 can be applied to other global health initiatives, including:

• High-Level Political Commitment: The commitment of Health Ministers was essential at every stage, and the ongoing support from WHO Member States through decisions and resolutions at the Executive Board and World Health Assembly provided critical backing for the initiative.
• Centralized and Collective Decision-Making: Centralizing decision-making within governance bodies, while ensuring decisions were made collectively, enabled coherent messaging, fast-paced decision-making, and strong ownership. Aligning the process with the advice of WHO scientific advisory bodies, such as SAGE and GACVS, helped ensure legitimacy and acceptance of decisions.
• Funding and Investment Model: Securing guaranteed funding from the outset through a sole funder created favorable conditions for collective decision-making. This approach facilitated a focus on quality and speed, ensuring efficiency and effectiveness in advancing the initiative.
• Adaptive and Innovative Models of Collaboration: Governance structures evolved throughout the process—from a consortium of researchers to the integration of the broader GPEI partnership and the establishment of the nOPV2 Working Group. Sub-groups and memberships were adjusted as needed, even if it meant making difficult decisions to ensure the initiative’s success.
• The Multifaceted Role of the Bill & Melinda Gates Foundation (BMGF): BMGF played a critical role as both a funder and a provider of an institutional framework. Its contributions were pivotal in managing complex processes, particularly in working with regulators and engaging with countries to ensure successful rollout and coordination.

Conclusions: 

In the past, 365,000 children were paralyzed by polio every year—an alarming statistic that highlights the immense scale of the challenge. The progress we’ve made is nothing short of a remarkable success story. However, there is a risk that, due to the difficulty of the task, the delays, and the cost overruns, we may be tempted to give up. But if we stay committed and do it right, not only will the world succeed in eradicating polio, but we will also strengthen systems for routine vaccination, improve access to clean water and sanitation, and build public confidence in the ability of health systems to deliver. Eradication represents the pinnacle of both equity and sustainability—an achievement that benefits everyone, everywhere, for generations to come.

Bibliography:

• 1. Polio Global Eradication Initiative. https://polioeradication.org/.
  2. Polio Global Eradication Initiative: Polio Endgame Strategy. https://polioeradication.org/who-we-are/polio-endgame-strategy-2019-2023/
  3. Polio eradication strategy 2022–2026: delivering on a promise. https://www.who.int/publications/i/item/9789240031937
  4. WHO Prequalification of Medical Products: Polio Vaccine, Novel Oral (nOPV2) (Monovalent type 2. https://extranet.who.int/prequal/vaccines/polio-vaccine-novel-oral-nopv-monovalent-type-2
  5. WHO Safety profile of nOPV2 vaccine. https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/poliovirus-vaccines
  6. Polio Global Eradication Initiative: GPEI press release on nOPV2 prequalification under its Emergency Use Listing.