nOPV2 Frequently Asked Questions

To better address the evolving risk of type 2 circulating vaccine-derived poliovirus (cVDPV2), GPEI partners are working to deploy an additional innovative tool – novel oral polio vaccine type 2 (nOPV2). The vaccine is a modified version of the existing type 2 monovalent OPV (mOPV2), that clinical trials have shown provides comparable protection against poliovirus while being more genetically stable and less likely to revert into a form which can cause paralysis. The vaccine’s increased genetic stability means there is a reduced risk of seeding new cVDPV2 outbreaks compared to mOPV2.

A dedicated consortium of experts has been working on nOPV2 development since 2011. A phase I and two phase II trials have been completed with the vaccine tested in adults, young children and infants.

The first in-human clinical trial was conducted in 2017 at the University of Antwerp and found nOPV2 to be safe and effective in providing immunity against polio. The Lancet published these findings in June 2019.

Key phase II trials are complete, and early analysis of the data shows similarly encouraging results for safety, immunogenicity and genetic stability of nOPV2.

Collectively, the clinical trials provide a robust evidence base around the expected behaviour of the vaccine in humans.

nOPV2 is being considered for deployment under WHO’s Emergency Use Listing procedure (EUL) to enable rapid field availability.

The EUL involves careful and rigorous analysis of existing data to enable early, targeted use of  unlicensed products for a Public Health Emergency of International Concern – which polio has been since 2014. The mechanism has been used in the past to facilitate the emergency use of diagnostic products for both Ebola and Zika virus.

WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) endorsed accelerated clinical development of nOPV2 and its assessment under EUL in October 2019.

Based on promising data from clinical trials, and the public health emergency that cVDPV2 constitutes, preparations are underway for at-risk production of 100 million doses of nOPV2 by as early as quarter 3 2020 to ensure it can be deployed immediately once relevant regulatory approvals for use are obtained.

GPEI expects that 200 million doses of the new vaccine will be ready by the end of 2020, and is monitoring the situation, especially in light of COVID-19.

The GPEI has developed criteria for initial use of nOPV2 and these plans were endorsed by SAGE in April 2020. Several epidemiological and logistical factors are considered to ensure an optimal system for supply of vaccine, once nOPV2 is recommended for use under an EUL. These include ensuring nOPV2 is the only oral polio vaccine used in a geographic area where cVDPV2s are present and that the country in question has robust disease surveillance to ensure optimal analysis of the vaccine’s performance.

A prioritization scheme for distribution of the vaccine after the initial use period is currently being developed.

Generating data on safety, immunogenicity and genetic stability of nOPV2 are a top priority of the GPEI and the vaccine will be subject to continued benefit-risk analysis, guided by clear and established ethical guidelines.

Even after meeting rigorous EUL criteria for safety and efficacy, nOPV2’s performance in the field will be closely monitored in line with EUL standards.

Post-deployment monitoring is a requirement once a WHO EUL recommendation for use is granted. This is a risk-based process to track new product performance in the field. WHO’s Regulation and Prequalification Department (RPQ) will carefully examine reports on safety, effectiveness and other relevant data that may impact the validity of the listing status. The sources of such information will be primarily based on existing surveillance mechanisms in affected countries and on post-listing surveillance commitments of the manufacturer, set as conditions for the listing.

All countries using nOPV2 based on a WHO EUL recommendation for use will need to meet the post deployment monitoring requirements as outlined in the listing conditions.

Outbreak control and case prevention will be the measures to gauge nOPV2’s effectiveness. In addition to outbreak control, as the vaccine has been designed to be more genetically stable than mOPV2, lower rates of new emergences of VDPV as a result of the vaccine’s use is also expected.

Initial use of nOPV2 in countries affected by cVDPV2 will be limited to immunization with nOPV2 only. This is important to be able to adequately monitor the vaccine’s performance.

After the initial use period, nOPV2 can be administered alongside other vaccines as appropriate to the country setting. For example, bivalent oral polio vaccine (bOPV) which protects against types 1 and 3 poliovirus, and inactivated polio vaccine (IPV) which provides immunity against all three strains but does not stop transmission of the virus. bOPV and IPV will continue to be used in global routine immunization programmes and in mass supplementary immunization activities/campaigns in countries affected/at risk of type 1 wild poliovirus.

Having a number of vaccine options and use strategies gives us the best chance to achieve and sustain a polio-free world.

Polio outbreak responses – for wild or vaccine-derived polioviruses  ̶  generally consist of multiple immunization rounds, needed to stop transmission. The quality of rounds determines how much vaccine is needed. It is possible to stop an outbreak with three to four high-quality rounds.

The production of nOPV2 is expected to be similar to production of the existing type 2 oral polio vaccine, which means that over the long-term, prices could approach those for mOPV2. Details need to be finalized based on experience from commercial production and release, and scale of use of the vaccine, among other factors.

GPEI has a history of successfully encouraging vaccine uptake and is committed to working across all levels of health systems and communities to ensure confidence in all polio vaccines.

The programme is working with Member States where nOPV2 could be approved for use to ensure there is consensus among relevant in-country decision makers and health officials for use of the vaccine to stop cVDPV2 outbreaks. GPEI is also conducting research in focus countries to better understand potential challenges and barriers in communicating with communities about the new vaccine.

Health care providers are the main opinion leaders on health issues for parents and GPEI is already raising awareness and working to garner support at all levels of the public health community for potential nOPV2 rollout.

The programme has a long-standing commitment to understanding the underlying reasons for non-vaccination  ̶  including misinformation or doubts among parents, caregivers and community leaders  ̶  to ensure its communications are tailored for local audiences in order to build trust.

If nOPV2 proves to be as effective as anticipated at stopping cVDPV2 outbreaks, it would be a significant development for eradication efforts; however, this alone will not achieve a polio-free world.

Important to remember is that vaccines are only as good as the number of people they reach – in order to eradicate all forms of polio, and maintain eradication, countries must prioritize maintaining strong disease surveillance and improving immunization campaign quality to ensure all children are reached with polio vaccines.

The Bill & Melinda Gates Foundation has funded all development and clinical trials of nOPV2 to date, working closely with GPEI partners throughout the process to ensure resources are going toward a tool that could prove critical to helping end all forms of polio.

Based on promising data from clinical trials, and the public health emergency that cVDPV2 constitutes, the Foundation is funding at-risk production of 100 million doses of nOPV2 to ensure it can be deployed immediately following regulatory approvals.

nOPV for types 1 and 3 poliovirus, called nOPV1 and nOPV3, are in preclinical development and first in-human trials with these vaccines are expected to begin in late 2020 – early 2021.

Should clinical trials with these vaccines prove successful, nOPV1 and nOPV3 could be kept in stockpiles and used in case of future cVDPV1 and cVDPV3 outbreaks respectively; however, there is no plan to replace currently used bOPV in routine immunization programmes.

WHO is engaging its regional regulatory networks to sensitize National Regulatory Authorities (NRAs) on nOPV2 and its anticipated benefits based on data from clinical studies to date. Individual NRAs have been invited to participate in the EUL review and are being engaged to help facilitate the necessary country-level decision process for authorization for use.

Post-deployment surveillance commitments are defined in a post-deployment monitoring plan, which the manufacturer of nOPV2 has developed together with the GPEI. WHO’s prequalification team is currently reviewing the plan. The plan contains elements relating to general safety (adverse events following immunization  ̶  AEFI) monitoring, vaccine associated paralytic poliomyelitis (VAPP), acute flaccid paralysis (AFP) surveillance, environmental surveillance (where feasible) and vaccine effectiveness.

For many countries, the level and quality of data captured by existing surveillance systems, i.e. AFP surveillance, environmental surveillance and AEFI safety reporting systems, should be sufficient to meet requirements. However for countries where these systems or weak, or are not yet in place, additional measures may need to be taken to enhance surveillance sensitivity. GPEI will be working with high risk countries in advance of nOPV2 rollout to assess their readiness to meet the post-deployment requirements and to identify plans to address any gaps.

If no quality/safety issues are identified with nOPV2 post deployment, the EUL status of the vaccine may be maintained. If quality/safety issues are identified, WHO may revoke the EUL recommendation for use of nOPV2.

Generating data on safety, immunogenicity and genetic stability of nOPV2 is a top priority for the GPEI. The ultimate goal is for the vaccine to pass through WHO prequalification.

Further nOPV2 trials will be conducted. Phase III clinical trials and additional nOPV2 studies are being planned, with the ultimate goal for nOPV2 to pass through WHO prequalification.

nOPV2 is an oral vaccine. It is administered via two drops, given into the mouth of the child. This is the same as for other oral polio vaccines.

nOPV2 will look similar to mOPV2. The liquid is the same in colour and the same type of dropper dispensers will be used. Differences will include the packaging and vaccine vial labeling as well as the size of the vaccine vial. Different labeling and packaging design is important to differentiate the two vaccines, although they will not be used together in the field. For vial size, nOPV2 will come in a larger 50-dose vial as opposed to the typical 20-dose vial.

Outbreak response with nOPV2 will be conducted in the same way as outbreak response using mOPV2. However, as nOPV2 does not carry the same risk of seeding new outbreaks, the handling of vaccine vials following supplementary immunization activities could be slightly different, and relevant guidelines with necessary details will be prepared by GPEI.

nOPV2 will come in 50-dose vials, which are larger in size than traditional 20-dose OPV vials. GPEI is currently investigating the feasibility of including a Vaccine Vial Monitor (VVM) for nOPV2, for monitoring of heat exposure over time and vaccine potency.

There is potential that mOPV2 will still be used after nOPV2 receives a WHO EUL recommendation for use. This decision depends on several factors, including sufficient supply of nOPV2, evolving epidemiology of cVDPV2s, and the ability of countries to authorize the use and import of nOPV2 in a timely manner and meet the post-EUL requirements. The polio programme would likely stop using mOPV2 in outbreak response prior to nOPV2 prequalification if nOPV2 proves successful in outbreak response and to carry a lower risk of seeding outbreaks, as anticipated, and if there is sufficient stockpile of the vaccine. This would mean that nOPV2 replaces mOPV2 for cVDPV2 response.

The full impact of the global COVID-19 situation on nOPV2 manufacture and rollout remains to be seen. The program is preparing for possible delays, though nOPV2 continues to be a top priority and preparatory work will continue at full speed so that countries facing cVDPV2 outbreaks are able to respond with nOPV2, if desired, once their national COVID-19 situation stabilizes.