Results
pneumonia, hepatitis A/B, vomiting, watery diarrhoea, gastrointestinal disorders
PNEUMONIA, ADVERSE EVENTS, VIRAL SHEDDING, SECONDARY, GASTROINTESTINAL DISORDERS
Between Sept 21, 2020, and Aug 16, 2021, we screened 334 newborn infants, of whom three (<1%) were found to be ineligible and one (<1%) was withdrawn by the parents; the remaining 330 (99%) infants were assigned to the two study groups (220 [67%] assigned to nOPV2 and 110 [33%] to placebo; Trial profilenOPV2=novel oral poliovirus vaccine type 2.Demographics of study participants at enrolment (intention-to-treat population)Data are n (%), n/N (%), or mean (SD). nOPV2=novel oral poliovirus vaccine type 2.Other vaccines included one case of a prophylactic dose of hepatitis A/B at birth.We found that nOPV2 was as well tolerated as placebo; adverse events were reported in 183 (83%) of 220 nOPV2 recipients and in 90 (82%) of 110 placebo recipients (Rates of solicited adverse events within 7 days of the first and second doses in the nOPV2 and placebo groupsSeverity shown only for placebo group as all adverse events in the nOPV2 group were reported as mild. nOPV2=novel oral poliovirus vaccine type 2.Most of the severe unsolicited adverse events were also considered to be serious adverse events. In 16 participants we reported 19 serious adverse events, none of which were considered to be related to study treatment when assessed by the study investigators. With the exception of one infant in the nOPV2 group who was diagnosed with severe pneumonia 5 days after the second vaccination, all serious adverse events occurred more than 9 days after receiving a first or second dose of nOPV2 or placebo. We reported no adverse events of special interest, but when unsolicited adverse events were specifically analysed for gastrointestinal disorders that could potentially be related to an oral vaccine we found six adverse events in nOPV2 recipients: five mild cases (one of vomiting, two of abdominal distension, and two of watery diarrhoea) and one umbilical hernia described as moderate in severity. In placebo recipients we found one case of mild watery diarrhoea. Investigators did not consider that any of these gastrointestinal disorders were related to vaccination.Most newborn infants had neutralising antibodies against polioviruses at birth, presumed due to transfer of maternal antibodies. Seroprotective titres (≥1:8) were present in 204 (93%) of 220 infants in the nOPV2 group and 102 (93%) of 110 in the placebo group (Seroconversion and seroprotection rates for type 2 poliovirus neutralising antibodies (per protocol)Data are n/N (%; 95% CI). nOPV2=novel oral poliovirus vaccine type 2.Only measured in participants whose baseline titre was low enough to allow measurement of a four-times increase without exceeding the maximum titre of 1448. All participants qualified at week 8.Neutralising antibody responses to two doses of nOPV2 or placeboLarge panel shows GMTs against poliovirus type 2 and smaller panels show GMTs against poliovirus types 1 and 3 (Seroconversion resulted in 214 (99%) of 217 vaccine recipients having seroprotective titres (≥1:8) at 8 weeks, after this proportion had initially reduced to 198 (90%) of 219 vaccine recipients at week 4 (Titres of neutralising antibodies against poliovirus types 1 and 3 decreased from birth to week 8 in both nOPV2 and placebo groups, with no notable differences between groups (With respect to the secondary objective of viral shedding, as expected, we found no RT-PCR-detectable shedding of poliovirus types 1, 2, or 3 in baseline stool samples; however, 2 weeks after the first dose of nOPV2, type 2 viral shedding was detectable in 114 (52%) of 219 nOPV2 recipients (Rates of faecal viral shedding by type assessed by real-time RT-PCR over the course of the study (per protocol)CCID50=cell culture infectious dose of 50%. IPV=inactivated poliovirus vaccine. nOPV2=novel oral poliovirus vaccine type 2. OPV=oral poliovirus vaccine.n=110 at baseline and week 2, n=108 at weeks 4 and 6, n=105 at week 8, and n=107 at weeks 10 and 12.The peak positivity of 17% (38/219) in the CCIDWe found two instances each of shedding of poliovirus types 1 and 3 before the administration of bivalent OPV at week 8, with stool samples from two different placebo recipients being PCR positive for type 1 at weeks 6 and 8, and two nOPV2 vaccinees with samples PCR positive for type 3 at week 8. Following doses of bivalent OPV and fractional IPV administration at week 8, poliovirus types 1 and 3 were detected by PCR, but with a small difference in the type 1 shedding in nOPV2 and placebo recipients. 2 weeks after bivalent OPV administration, 77 (72%) of 107 infants in the placebo group were shedding PCR-detectable type 1 poliovirus, which decreased to 43 (40%) of 107 by 12 weeks. In the nOPV2 group, these rates were lower, at 57% (124/219) at week 10 and 27% (60/219) at week 12. Shedding of type 3 poliovirus was similar in both groups and appeared to last longer than that of type 1. Thus, type 3 poliovirus was detectable in 146 (67%) of 219 infants in the nOPV2 group and 71 (66%) of 107 in the placebo group at week 10 and was still detectable in 122 (56%) infants in the nOPV2 group and 60 (56%) in the placebo group at week 12.