Two novel live attenuated monovalent oral type-2 poliovirus vaccine (OPV2) candidates were found to be safe and immunogenic in adults immunized by the Sabin inactivated polio vaccine (IPV), according to a study published in The Lancet. Further, data from the phase 1 trial support developing the vaccines with the aim of maintaining the global eradication of neurovirulent type-2 polioviruses.
Wild polio viruses have almost been eradicated by use of OPV and IPV. These OPV2 vaccine candidates were developed to minimize the risk for outbreaks from vaccine-derived polioviruses. The OPV2 candidates are more genetically stable than existing OPVs, and they have a lower risk for reversion to neurovirulence. This double-blind, single-center phase 1 trial represents the first human-testing of these 2 candidates, with the aim of evaluating the vaccines’ safety and immunogenicity, the presence and extent of fecal shedding of poliovirus, and the neurovirulence of shed virus.
To minimize the risk of environmental release, participants were isolated in a containment facility built for this purpose at the University of Antwerp Hospital in Belgium. Participants were recruited through local advertising and were aged 21 to 50, in good health, had been previously vaccinated with IPV, and would have no contact with unvaccinated or immunosuppressed individuals until either 3 consecutive stool samples demonstrated no polio viron particles, or 28 days post-vaccination.
Of 30 participants, 15 were randomly assigned into either the vaccine candidate 1 group (S2/cre5/S15domV/rec1/hifi3) or the vaccine candidate 2 group (S2/S15domV/CpG40), and all participants were monitored for immune responses, adverse events, and fecal shedding of the virus for 28 days. Shed virus isolates were tested for genetic stability of attenuation. Primary outcomes were type and incidence of serious adverse events and severe events, the proportion of participants showing fecal shedding, the time to cessation of fecal viral shedding, the cell culture infective dose of virus shed in virus-positive stools, and the combined index of duration, prevalence, and quantity of fecal shedding in all participants.
Both OPV2 candidates were shown to be immunogenic and increased the median blood titer of serum-neutralizing antibodies. After vaccination, all participants were seroprotected. Both vaccine candidates had acceptable tolerability and caused no serious adverse events during the study. However, a total of 8 severe adverse events were experienced by 6 of the 15 (40%) participants who received vaccine candidate 1; 9 of the 15 participants (60%) receiving candidate 2 experienced a total of 12 severe adverse events. The most common of these severe adverse events were temporary increases of blood creatinine phosphokinase and aspartate aminotransferase concentrations; these were not accompanied by clinical signs or symptoms. Most events resolved spontaneously or with standard treatment during the study period.
Vaccine virus was detected in all 15 (100%) stool samples of participants receiving candidate 1, and in 13 of 15 (87%) of participants receiving candidate 2. Vaccine poliovirus fecal shedding ceased at a median of 23 days (interquartile range [IQR] 15-36) after vaccine candidate 1 administration and 12 days (IQR 1-23) after candidate 2 administration. Total shedding, which was defined as the estimated median shedding index (50% cell culture infective dose/g), was greater with vaccine candidate 1 than candidate 2 across all trial participants 2.8 vs 1.0 (95% CI, 1.8-3.5 vs 95% CI, 0.7-1.6, respectively). Reversion to neurovirulence, as assessed by paralysis in transgenic mice, was low in isolates from mice vaccinated with both candidates, and sequencing of the shed virus indicated no loss of attenuation in domain V of the 5′-untranslated region, the primary site of reversion in OPV.
Study investigators concluded that this trial demonstrated the 2 novel OPV2 candidates may provide a more genetically stable alternative to the current Sabin monovalent OPV2 stockpiled for control of [circulating vaccine-derived type-2 polio virus] outbreaks. Further, the researchers concluded that “[with] all live type-2 polioviruses withdrawn from routine immunisation use, the global population is now reliant on IPV to provide immunity against type-2 polioviruses. The limited primary intestinal immunity provided by IPV requires that an outbreak response must rely on Sabin oral live-attenuated poliovirus vaccines to interrupt person-to-person transmission… [and]novel candidate vaccines such as those we have tested could be crucial components of efforts to ensure complete and permanent global eradication of poliovirus type-2.”
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