Two new polio vaccines show promise for both young, old

Two separate studies underline the safety and tolerability of two new type 2 oral poliovirus vaccines (OPV2) – the novel OPV2-c1 and OPV2-c2 – in infants, children, and adults.

Despite the global suppression of wild type 2 poliovirus and global withdrawal of OPV2s, type 2 polio outbreaks continue to rise due to cVDPV2*, especially in areas with low immunization coverage. [MMWR Morb Mortal Wkly Rep 2016;65:934-938; J Infect Dis 2014;210 suppl 1:S283-S293] Initial efforts to control outbreaks were rolled out using monovalent OPV2. “[However, this] risks seeding further cVDPV2 because of its inherent tendency to lose attenuating mutations,” noted the team evaluating the adult cohort.

The WHO classified the upsurge in cVDPV2 cases as a PHEIC** in 2014, hence the GPEI*** response to develop new vaccines. [https://polioeradication.org/wp-content/uploads/2020/04/Strategy-for-the-response-to-type-2-circulating-Vaccine-Derived-Poliovirus-20200406.pdf, accessed March 22, 2021] “This unique epidemiological situation necessitates an urgent need for the development and introduction of more genetically stable [OPVs] to respond to the global emergency,” they added. The situation is further compounded by the temporary disruption of immunization drives due to the ongoing COVID-19 pandemic. [Risk Anal 2021;41:329-348]

As such, new OPV2s were engineered to be more genetically stable than monovalent OPV2. [https://polioeradication.org/wp-content/uploads/2020/04/Strategy-for-the-response-to-type-2-circulating-Vaccine-Derived-Poliovirus-20200406.pdf, accessed March 22, 2021] “[These] are the first new OPV strains in advanced clinical development in ~60 years … [They] could be an important addition to our resources against poliovirus given the current epidemiological situation,” noted the team evaluating the younger cohort.­

 

Healthy adults

This study comprised two trials in Belgium on adults aged 18–50 years with prior polio vaccinations (OPV and IPV^#). The first, a phase IV historical control study, randomized 100 adults 1:1 to receive one or two doses of monovalent OPV2^##. In the second phase II study (S2), randomization was as follows: Of 200 adults with prior OPVs, 100 were randomized 1:1 to receive one or two doses of OPV2-c1; the other 100 were randomized 1:1 to receive one or two doses of OPV2-c2. Those who have previously received IPVs (n=50) were randomized 1:1:1 to receive two doses of either novel OPV2-c1, OPV2-c2, or placebo. One of the coprimary endpoints was the safety of the two novel OPV2s based on serious and severe adverse events (AEs) 28 days following the first dose. [Lancet 20212;397:39-50]

Both trials reported no vaccine-related withdrawals, fatal conditions, or deaths. Of the four serious AEs in S2, only one was presumed vaccine-related. These underscore the safety and tolerability of the two novel OPV2s in this patient setting.

Immunogenicity-wise, seroprotection at day 28 with both novel OPV2s (100 percent) mirrored that of the monovalent OPV2 they were designed to replace (97 percent), with similar viral shedding profiles and improved genetic stability after intestinal passage.

“[T]he data thus far suggests that the goal of developing more genetically stable, attenuated OPV2s with no effect on the immunogenicity has been achieved,” said the researchers. “[Nonetheless,] further study is underway to confirm the objective of mitigating reacquisition of neurovirulence by these novel OPV2 vaccines.”

 

Children, infants

With the eradication of OPV2s, children and infants rely on IPVs to acquire immunity against polio. However, given the minimal intestinal mucosal immunity with IPVs, preventing cVDPV transmission requires live OPVs. [Science 2020;368:401-405]

This study thus explored two trials looking at healthy children (aged 1–4 years) and infants (aged 18–22 weeks) in Panama who had received at least one polio vaccine. In the historical control phase IV study (S3), 50 children received two doses of the monovalent OPV2^## 28 days apart, while 110 infants received one dose. In the phase II study (S4), 100 children received two high doses of either OPV2-c1 or OPV2-c2 28 days apart, while 574 infants received one low or high dose of either novel OPV2. The coprimary endpoints were the safety of the novel OPV2s in all participants, and immunogenicity in infants, by day 28. [Lancet 2021 2;397:27-38]

At said timepoint, the only serious AE reported in children was associated with the novel OPV2-c2 (high-dose); in infants, 19 were reported (n=1 and 18 in S3 and S4, respectively). However, none were vaccine-related.

“[There was also] no consistent pattern of grade 3/4 clinical laboratory abnormalities … at any point nor any clinically relevant abnormalities or changes in laboratory assessments in children or infants after vaccination in either study,” noted the researchers. The atypical blood cell counts prior to vaccination were also transient.

In terms of immunogenicity in infants by day 28, seroprotection rates were 94 percent in S3 and between 91 and 95 percent in S4 (any dose of either novel OPV2). “[These imply that] all vaccinations resulted in high seroprotection [after one dose],” the researchers explained.

These support the favourable safety and tolerability of low and high doses of the two novel OPV2s in previously vaccinated children and infants. “The present data are the only information available to our knowledge to inform policymakers, regulators, and healthcare providers on the use of the novel vaccine in the age group considered most susceptible to poliovirus transmission,” they stressed.

“[Moreover,] these findings … contributed to the selection of the novel OPV2-c1 as the first new vaccine to be listed under the WHO Emergency Use Listing procedure for use in cVDPV2 outbreaks,” said the researchers. “Our data are essential to inform the ongoing policy and regulatory assessments to enable the proposed rollout of novel OPV2-c1 in 2020 and 2021.”

 

A step forward in the fight against polio

“Ultimately, the development of novel OPVs could lead to an easier-to-deliver and more cost-effective poliovirus vaccine option than IPV for countries that rely on OPV,” said Professor Kimberly Thompson from Kid Risk, Orlando Florida, US, in a separate commentary. [Lancet 2021;397:2-3]

“The results from these studies and the Emergency Use Listing represent … promising next steps towards the future of global poliovirus control and eradication using better performing OPV strains … [These are] exciting steps for a world that already needed more OPV2 before the COVID-19 pandemic,” added Thompson.