Discussion
VIRUS, ADVERSE EVENTS, EVENT, ADVERSE EVENT, EVENTS
We found similar tolerability profiles in the nOPV2 and placebo groups, with only mild solicited adverse events and no related serious adverse events or adverse events of special interest reported. Solicited adverse event rates after nOPV2 and placebo were higher after second doses than after first doses, representing either an increase in the detection rate of such events in children aged 4–5 weeks compared with 0–10 days, or a true increase in the event rate. The immune response was shown against a background of waning maternal neutralising antibodies, evidenced in the placebo group, in which the seroprotection rate decreased from 93% at baseline to 56% at week 8. The 90% seroconversion rate elicited by two doses of nOPV2 resulted in 99% of nOPV2 recipients having seroprotective titres at week 8. Furthermore, in those infants who did not have protective maternal antibodies at birth, vaccination with nOPV2 resulted in 100% seroconversion after two doses, indicating that all infants had protective titres.Following the global withdrawal of OPV2 vaccines,Proportions of infants shedding type 2 virus 2 weeks after the first and second doses of nOPV2 were similar to the proportions shedding types 1 and 3 viruses 2 weeks after the first dose of bivalent OPV. These proportions declined progressively through weeks 4, 8, and 10, and only one infant was still shedding type 2 virus by week 12.Amounts of virus excreted were low, with only 17% at week 2 and 14% at week 6 shedding sufficient virus to be measurable by culture, 2 weeks after the nOPV2 doses, indicating no increased transmission risk for those receiving nOPV2 before any other poliovirus vaccination, relative to those previously receiving IPV.However, our data correspond well with previous observations of nOPV2 shedding in the phase 2 study in previously vaccinated infants in which infants who received nOPV2 displayed similar shedding characteristics to those who received monovalent OPV2 7 days after vaccination but then a significantly lower rate of shedding than monovalent OPV2 4 weeks after vaccination.We have no data on whether nOPV2 interferes with the viral replication or immune responses to Sabin types 1 and 3, as would occur with the later administration of bivalent OPV in routine vaccination schedules. This gap could be seen as a limitation of the present study, because we did not investigate the immune responses to bivalent OPV or the fractional dose IPV, but this question is being investigated in a parallel study (Concerns in industrialised nations where poliovirus is considered to be eliminated following the detection of cVDPV2 in sewage in London, UK,Data from this study support the use of nOPV2 in vulnerable vaccine-naive newborn infants, who might be at particular risk during cVDPV2 outbreaks. nOPV2 has already been widely implemented in outbreak responses, with over 450 million doses distributed under the WHO EUL procedure, with no restriction on the age of recipients.