Safety of the novel oral poliovirus vaccine type 2 (nOPV2) in infants and young children aged 1 to <5 years and lot-to-lot consistency of the immune response to nOPV2 in infants in The Gambia: a phase 3, double-blind, randomised controlled trial.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) has been engineered to improve the genetic stability of Sabin oral poliovirus vaccine (OPV) and reduce the emergence of circulating vaccine-derived polioviruses. This trial aimed to provide key safety and immunogenicity data required for nOPV2 licensure and WHO prequalification. METHODS: This phase 3 trial recruited infants aged 18 to <52 weeks and young children aged 1 to <5 years in The Gambia. Infants randomly assigned to receive one or two doses of one of three lots of nOPV2 or one lot of bivalent OPV (bOPV). Young children were randomised to receive two doses of nOPV2 lot 1 or bOPV. The primary immunogenicity objective was to assess lot-to-lot equivalence of the three nOPV2 lots based on one-dose type 2 poliovirus neutralising antibody seroconversion rates in infants. Equivalence was declared if the 95% CI for the three pairwise rate differences was within the -10% to 10% equivalence margin. Tolerability and safety were assessed based on the rates of solicited adverse events to 7 days, unsolicited adverse events to 28 days, and serious adverse events to 3 months post-dose. Stool poliovirus excretion was examined. The trial was registered as PACTR202010705577776 and is completed. FINDINGS: Between February and October, 2021, 2345 infants and 600 young children were vaccinated. 2272 (96·9%) were eligible for inclusion in the post-dose one per-protocol population. Seroconversion rates ranged from 48·9% to 49·2% across the three lots. The minimum lower bound of the 95% CIs for the pairwise differences in seroconversion rates between lots was -5·8%. The maximum upper bound was 5·4%. Equivalence was therefore shown. Of those seronegative at baseline, 143 (85·6%) of 167 (95% CI 79·4-90·6) infants and 54 (83·1%) of 65 (71·7-91·2) young children seroconverted over the two-dose nOPV2 schedule. The post-two-dose seroprotection rates, including participants who were both seronegative and seropositive at baseline, were 604 (92·9%) of 650 (95% CI 90·7-94·8) in infants and 276 (95·5%) of 289 (92·4-97·6) in young children. No safety concerns were identified. 7 days post-dose one, 78 (41·7%) of 187 (95% CI 34·6-49·1) infants were excreting the type 2 poliovirus. INTERPRETATION: nOPV2 was immunogenic and safe in infants and young children in The Gambia. The data support the licensure and WHO prequalification of nOPV2. FUNDING: Bill & Melinda Gates Foundation.

Persistence of immunity following a single dose of inactivated poliovirus vaccine: a phase 4, open label, non-randomised clinical trial.

BACKGROUND: The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. METHODS: In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ2 to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. FINDINGS: From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. INTERPRETATION: A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. FUNDING: WHO and Rotary International.

Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial.

BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention.

Poliovirus antibodies following two rounds of campaigns with a type 2 novel oral poliovirus vaccine in Liberia: a clustered, population-based seroprevalence survey.

BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was administered in Liberia in response to an outbreak of circulating vaccine-derived poliovirus type 2 (cVDPV2) in 2021. We conducted a serological survey of polio antibodies after two national campaigns with nOPV2. METHODS: This clustered, cross-sectional, population-based seroprevalence survey was conducted in children aged 0-59 months, more than 4 weeks after the second nOPV2 vaccination round. We used a clustered sampling method in four geographical regions of Liberia, followed by a simple random sampling of households. One eligible child was randomly selected per household. Dried blood spot specimens were taken and vaccination history was recorded. The antibody titres against all three poliovirus serotypes were assessed using standard microneutralisation assays done at the US Centers for Disease Control and Prevention in Atlanta, GA, USA. FINDINGS: Analysable data were obtained from 436 (87%) of 500 enrolled participants. Of these, 371 (85%) children were reported via parental recall to have received two nOPV2 doses, 43 (10%) received one dose, and 22 (5%) received no doses. The seroprevalence against type 2 poliovirus was 38·3% (95% CI 33·7-43·0; 167 of 436 participants). No significant difference was observed between type 2 seroprevalence in children aged 6 months or older who were reported to have received two doses of nOPV2 (42·1%, 95% CI 36·8-47·5; 144 of 342), one dose (28·0%, 12·1-49·4; seven of 25), or no doses (37·5%, 8·5-75·5; three of eight; p=0·39). The seroprevalence against type 1 was 59·6% (54·9-64·3; 260 of 436), and the seroprevalence against type 3 was 53·0% (48·2-57·7; 231 of 436). INTERPRETATION: Unexpectedly, the data showed low type 2 seroprevalence after two reported doses of nOPV2. This finding is probably affected by the lower oral poliovirus vaccine immunogenicity previously demonstrated in resource-limited settings, with high prevalence of chronic intestinal infections in children and other factors discussed herein. Our results provide the first assessment of nOPV2 performance in outbreak response in the African region. FUNDING: WHO and Rotary International.

A Survey to Assess Serological Prevalence of Poliovirus Antibodies in Areas With High-Risk for Vaccine-Derived Poliovirus Transmission in Chad.

BACKGROUND: World Health Organization African region is wild poliovirus-free; however, outbreaks of vaccine-derived poliovirus type 2 (VDPV2) continue to expand across the continent including in Chad. We conducted a serological survey of polio antibodies in polio high-risk areas of Chad to assess population immunity against poliovirus and estimate the risk of future outbreaks. METHODS: This was a community-based, cross-sectional survey carried out in September 2019. Children between 12 and 59 months were randomly selected using GIS enumeration of structures. Informed consent, demographic and anthropometric data, vaccination history, and blood spots were collected. Seropositivity against all 3 poliovirus serotypes was assessed using a microneutralization assay at Centers for Disease Control and Prevention, Atlanta, GA, USA. RESULTS: Analyzable data were obtained from 236 out of 285 (82.8%) enrolled children. Seroprevalence of polio antibodies for serotypes 1, 2, and 3 was 214/236 (90.7%); 145/236 (61.4%); and 196/236 (86.2%), respectively. For serotype 2, the seroprevalence significantly increased with age (P = .004); chronic malnutrition was a significant risk factor for being type 2-seronegative. INTERPRETATION: Poliovirus type 2 seroprevalence in young children was considered insufficient to protect against the spread of paralytic diseases caused by VDPV2. Indeed, VDPV2 outbreaks were reported from Chad in 2019 and 2020. High-quality immunization response to these outbreaks is needed to prevent further spread.