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The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) throughout many countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating [...]

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe. [ABSTRACT FROM AUTHOR]

Objective To evaluate the potential economic benefits of keeping a meningitis A vaccine at or near ambient temperature for up to 4 days during a mass vaccination campaign. Methods During a 10-day mass vaccination campaign against meningitis A in three regions of Chad in 2011, the costs associated with storage and transport of the vaccine in a traditional cold chain system were evaluated. A mathematical model was used to estimate the savings that could have been achieved if the vaccine had been stored at or near ambient temperature--in a'controlled temperature' chain --at the peripheral levels of the supply chain system. Findings The cost of the cold chain and associated logistics used in the campaign in Chad was 0.24 United States dollars (US$) per person vaccinated. In the modelled scenario for a controlled temperature chain, however, these costs dropped by 50% and were estimated to be only US$ 0.12 per person vaccinated. Conclusion The implementation of a 'controlled temperature' chain at the most peripheral levels of the supply chain system--assuming no associated loss of vaccine potency, efficacy or safety--could result in major economic benefits and allow vaccine coverage to be extended in low-resource settings. Objectif Evaluar les avantages economiques potentiels de la conservation d'un vaccin contre la meningite A a temperature ambiante ou a une temperature proche de la temperature ambiantejusqu'a 4 jours, au cours d'une campagne de vaccination de masse. Methodes Au cours d'une campagne de vaccination de masse de 10 jours contre la meningite A dans trois regions du Tchad en 2011, on a evalue les couts associes au stockage et au transport du vaccin dans un systeme de chaine du froid traditionnel. Un modele mathematique a ete utilise pour estimer les economies qui auraient pu etre realisees si les vaccins avaient ete conserves a temperature ambiante ou a une temperature proche de la temperature ambiante--dans une chaine de <>--a des niveaux peripheriques du systeme de la chaine d'approvisionnement. Resultats Le cout de la chaine du froid et de la logistique associee utilisees dans la campagne de vaccination au Tchad etait de 0,245 par person ne vaccinee.Toutefois, dans le scenario modelise d'une chaine de temperature controlee, ces couts ont chute de 50% et ont ete estimes a seulement 0,12$ par personne vaccinee. Conclusion La mise en oeuvre d'une chaine de <> aux niveaux les plus peripheriques du systeme de chaine d'approvisionnement--en supposant qu'il n'y a aucune perte d'activite, d'efficacite ou de securite du vaccin associe--pourrait entrainer des avantages economiques importants et permettre l'extension de la couverture vaccinale dans des regions a revenu faible. Objetivo Evaluar los beneficios economicos potenciales de conservar las vacunas contra la meningitis A a (o a aproximadamente) temperatura ambiente durante un maximo de 4 dias en una campana de vacunacion masiva. Metodos Se evaluaron los costes asociados al almacenaje y transporte de la vacuna en un sistema de cadena de frio tradicional durante una campana de vacunacion masiva contra la meningitis A de 10 dias de duracion en tres regiones de Chad realizada en 2011. Se empleo un modelo matematico para estimar el ahorro que podria haberse logrado si la vacuna se hubiera almacenado a (o a aproximadamente) temperatura ambiente, en una cadena de <>, en los niveles perifericos del sistema de cadena de suministro. Resultados El coste de la cadena de frio y la logistica asociada usada en la campana en Chad fue de 0,24 dolares de los Estados Unidos (US$) por persona vacunada. En el modelo empleado para una cadena de temperatura controlada, sin embargo, estos costes descendieron un 50 % y se estimo que solo representaban US$ 0,12 por persona vacunada. Conclusion La aplicacion de una cadena de <> en los niveles mas perifericos del sistema de cadena de suministro, suponiendo que no haya perdida asociada de potencia de la vacuna, la eficacia o la seguridad, podria ofrecer importantes beneficios economicos y permitir que la cobertura de la vacuna se amplie en entornos de bajos recursos., Introduction It is difficult to keep vaccines cool in countries where the mean daytime temperature exceeds 30°C, electricity is unavailable in rural areas and the cold chain infrastructure is inadequate. [...]

In resource-constrained settings, getting vaccines safely and reliably to children in remote areas is a daily challenge. Exposure of vaccines to excessive heat or freezing temperatures, which often occurs in [...]

To address the evolving risk of circulating vaccine-derived poliovirus type 2 (cVDPV2), Global Polio Eradication Initiative (GPEI) partners are working closely with countries to deploy an additional innovative tool for outbreak response – novel oral polio vaccine type 2 (nOPV2). The World Health Organization's (WHO) Prequalification program issued an Emergency Use Listing (EUL) recommendation for nOPV2 on 13 November 2020. The WHO's EUL procedure was created to assess and list unlicensed vaccines, therapeutics and diagnostics to enable their use in response to a Public Health Emergency of International Concern (PHEIC). nOPV2 was the first vaccine to receive an EUL, paving the way for other emergency vaccines. In this report, we summarise the pathway for nOPV2 roll-out under EUL. [ABSTRACT FROM AUTHOR]

Following the global declaration of indigenous wild poliovirus type 2 eradication in 2015, the world switched to oral polio vaccine (OPV) that removed the type 2 component. This 'switch' included the widespread introduction of inactivated poliovirus vaccine and the creation of a stockpile of monovalent type 2 OPV (mOPV2) to respond to potential polio virus Type 2 (PV2) outbreaks and events. With subsequent detection of outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2), it was necessary to use this stockpile for outbreak response. Not only were more outbreaks detected than anticipated in the first few years after the switch, but the number of supplemental immunization activities (SIAs) used to stop transmission was often high, and in many cases did not stop wider transmission. Use of mOPV type 2 led in some locations to the emergence of new outbreaks that required further use of the vaccine from the stockpile. In the following years, stockpile management became a critical element of the cVDPV2 outbreak response strategy and continued to evolve to include trivalent OPV and genetically stabilized 'novel OPV type 2' vaccines in the stockpile. An overview of this process and its evolution is presented to highlight several of these management challenges. The unpredictable vaccine demand, fixed production and procurement timelines, resource requirements, and multiple vaccine types contributes to the complexity of assuring appropriate vaccine availability for this critical programmatic need to stop outbreaks. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors have declared that no competing interests exist.

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Isobel M. Blake, John Konz, Andrew Macadam, Javier Martin, John Modlin, and M. Steven Oberste report institutional support from the Bill and Melinda Gates Foundation. Andrew Macadam reports support for travel to consortium meetings from the Bill and Melinda Gates Foundation and PATH. Lester M. Shulman is an independent consultant for the McKing Consulting Corporation, an unpaid member of the Israel National Certification Committee for Polio, and a volunteer member of the Emergency Response Team for the current cVDPV3 polio outbreak in Israel. No other potential conflicts of interest were reported.