Two novel monovalent oral type-2 poliovirus (OPV2) vaccine candidates were found to be safe and immunogenic in adults who received the inactivated polio vaccine (IPV) previously, according to data published in The Lancet.
In a double-blind, single-center, phase 1 trial (ClinicalTrials.gov NCT03430349), investigators recruited 30 adults aged 18 to 50 years, all of whom had verified vaccination histories for IPV only. Investigators randomly assigned participants in a 1:1 ratio to receive a single dose of vaccine candidate 1 (S2/cre5/S15domV/rec1/hifi3) or candidate 2 (S2/S15domV/CpG40). These candidates contain live-attenuated serotype-2 poliovirus derived from a clone of a modified Sabin type-2 strain of the virus.
In addition, investigators isolated participants in a purpose-built containment facility to minimize the risk for environmental release of the novel OPV2 candidates. Participants monitored for adverse events, immune responses, and fecal shedding for the next 28 days and did not have any contact with individuals who were immunosuppressed or who were not vaccinated for the duration of fecal shedding at the end of the study. To evaluate vaccine efficacy, investigators assessed humoral immunogenicity by the presence of poliovirus type-2-specific serum neutralizing antibodies at days 0 and 28, as well as calculation of geometric mean titers, seroprotection, and seroconversion.
Both candidate vaccines had acceptable tolerability and no serious adverse events occurred during the study, although 8 severe events were reported in 6 participants who received vaccine candidate 1 and 12 events were reported in 9 participants who received vaccine candidate 2. Vaccine candidates 1 and 2 were both immunogenic and increased the median blood titer of serum neutralizing antibodies, with all participants achieving seroprotection after vaccination.
Vaccine virus was found in stools of 15 and 13 recipients of vaccine candidate 1 and 2, respectively. Shedding stopped at a median of 23 days (interquartile range 15-36 days) after administration of vaccine candidate 1 and 12 days (interquartile range 1-23 days) after vaccine candidate 2 administration. Total shedding was observed to be greater with vaccine candidate 1 than with candidate 2 across all participants, as determined by the estimated median shedding index (50% cell culture infective dose/g), 2.8 (95% CI, 1.8-3.5) vs 1.0 (95% CI, 0.7-1.6). Reversion to neurovirulence, assessed as paralysis of transgenic mice, was low in isolates from those vaccinated with both candidates. Sequencing of shed virus also indicated no loss of attenuation in domain V of the 5ʹ-untranslated region, which is the primary site of reversion in Sabin OPV.
The limitations to this work included the necessarily small number of participants, the use of the expected maximal dose of vaccine virus, and a lack of direct comparators for either candidate vaccine as a result of the global cessation of elective use of monovalent OPV2.
Investigators concluded that these 2 novel OPV2 candidates “have the potential to provide more genetically stable alternatives to the current Sabin monovalent OPV2 that is stockpiled for control of [circulating vaccine-derived poliovirus]2 outbreaks.” Further, novel candidates such as these could be crucial components of efforts to ensure global eradication of poliovirus type-2 due to the known reversion of Sabin monovalent OPV2 and ongoing evidence that it may have generated new circulating vaccine-derived polioviruses in some settings.
Van Damme P, De Coster I, Bandyopadhyay AS, et al. The safety and immunogenicity of two novel live attenuated monovalent (serotype 2) oral poliovirus vaccines in healthy adults: a double-blind, single-centre phase 1 study [published online June 4, 2019]. Lancet. doi:10.1016/S0140-6736(19)31279-6