Review 1: "Monitoring the Risk of Type-2 Circulating Vaccine-Derived Poliovirus Emergence during Roll-Out of Type-2 Novel Oral Polio Vaccine"

RR\ID Evidence Scale rating by reviewer:

• Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review: The authors described their efforts to monitor the risk of type-2 circulating vaccine-derived poliovirus emergence during roll-out of type-2 novel oral polio vaccine. They analyzed data on nOPV2 campaigns to estimate type-2 OPV-induced immunity in children under 5 years of age and surveillance data to estimate seeding date and classified cVDPV2 emergencies as Sabin- or novel-derived. The authors made 3 claims including:

1. About 98% of 1.19 billion doses of nOPV2 vaccines have been administered in Africa as of 1 August 2024.

2. There has been 18 cVDPV2 emergencies linked to nOPV2 as of 1 August 2024.

3. About 76 cVDPV2 emergencies would have occurred if we were using mOPV2 vaccines. 

The authors concluded that the use of nOPV2 has reduced the emergence of cVDPV2 by four-fold as it would have been if mOPV2 were used.

The introduction of the monovalent OPV2 to control outbreaks of cVDPV2 following the global switch from the trivalent OPV to bivalent OPV in 2016, accidentally led to more cVDPV2 than anticipated. This was because mOPV2, though efficient and effective, is genetically less stable and could revert to a neurovirulent form that could spread in under-immunized populations. Hence soon after its introduction, mOPV2 underwent sufficient genetic changes and circulated and caused paralysis in communities with poor sanitation and low vaccination coverage. In areas where multiple rounds of mOPV2 were conducted, high numbers of cVDPV2 outbreaks occurred making it a critical factor in persistence type 2 poliovirus transmission that even spread to other countries. The development and deployment of nOPV2 with a better genetic stability are intended to address this issue by reducing the likelihood of cVDPV2 seeding with less likely to revert into a form which can cause paralysis.

The claim by the authors that about 98% on nOPV2 vaccines have been administered in Africa is heavily supported by literature, most of which have been cited and evidenced in the manuscript. Similarly, the other two claims that 18 cVDPV2 emergencies linked to nOPV2 have been reported and that it would have been 76 if mOPV2 were to be used are also supported by the evidence in the manuscript. 

The data from clinical trials and field use have consistently demonstrated that nOPV2 provides comparable protection against poliovirus while being more genetically stable than mOPV2. This increased stability translates to a reduced risk of seeding new cVDPV2 outbreaks, making nOPV2 a valuable tool in the fight against polio. Furthermore, cVDPV2 emergencies linked to the monovalent oral poliovirus vaccine type 2 (mOPV2) occur at a rate of about one emergence per 10 million mOPV2 doses administered. However, the novel oral poliovirus vaccine type 2 (nOPV2) has a significantly lower rate of cVDPV2 emergencies, at approximately one emergence per 100 million doses. 

Therefore, the authors claims are supported by the evidence in the manuscript and also align with their conclusion that nOPV2 is genetically more stable than mOPV2.