Elizabeth Bailey Brickley

Background: Impact of prior inactivated poliovirus vaccine (IPV) doses on nasal and pharyngeal viral replication following subsequent poliovirus exposure remains unclear. Circulating vaccine-derived poliovirus detection in IPV-only countries necessitates better understanding of IPV's role in inducing nasal and pharyngeal mucosal immunity. Methods: This multicenter, randomized, open-label, parallel-group trial (9 November 2023–25 August 2024; ClinicalTrials.gov identifier: NCT05677256) was conducted in Bangladesh in 500 polio vaccine-naive infants aged 6–8 weeks. Two infant cohorts (vaccinated with 3 doses of either IPV or bivalent oral poliovirus vaccine [bOPV]) were challenged at 18–20 weeks with novel OPV type 2 (nOPV2). Pharyngeal and fecal viral shedding, and nasal, intestinal, and serum immune responses were measured post-nOPV2-challenge. Results: Poliovirus type 2 (PV2) pharyngeal shedding was minimal postchallenge (1.7% of IPV-vaccinated and 2.6% of bOPV-vaccinated infants). Nasal PV2-specific neutralizing antibody titers were higher in the IPV group post-nOPV2-challenge (day 14; geometric mean titers [GMT]: IPV, 7.5 [95% CI: 5.1–11.1] vs bOPV, 0.6 [95% CI: 0.3–1.2]). Stool PV2-specific neutralization titers were comparable at day 14 (GMT: IPV, 124.0 [95% CI: 54.7–281.0] vs bOPV, 127.3 [95% CI: 74.0–218.9]). Serum PV2 neutralizing antibody titers were consistently higher in IPV group, peaking at day 28 (GMT: IPV, 4347.4 [95% CI: 2378.2–7947.2] vs bOPV, 259.9 [95% CI: 115.5–584.9]). Conclusions: Novel OPV type 2 pharyngeal shedding was low following IPV or bOPV vaccination, whereas IPV induced higher nasal and serum, and comparable intestinal PV2-specific immunity, suggesting a potential role for IPV in poliovirus outbreak response in IPV-only settings.

Background: Mucosal immunity is critical for preventing poliovirus transmission. Despite evidence that infant immunisation protects against poliovirus infection into adulthood, the duration of vaccine-induced intestinal antibody responses remains poorly characterised. Methods: We evaluated poliovirus type-specific neutralising activity and immunoglobulin levels in stool and serum from children in Tanzania who completed routine poliovirus vaccine series (bivalent oral polio vaccine at birth, 6, 10, and 14-weeks, and inactivated polio vaccine at 14-weeks). The study included a longitudinal cohort with four visits over 6 months and a cross-sectional sample of children recruited 1 to 108-months after vaccine series completion. Potential modification by nutritional factors, gastrointestinal infections, and environmental enteropathy was explored. Results: Among 103 longitudinal and 246 cross-sectional participants enrolled, 33% and 18% had positive poliovirus type-1 (PV1) stool neutralisation, and 66% and 56% had positive poliovirus type-3 (PV3) neutralisation 1 month after vaccination. All were seropositive for PV1 and PV3 across timepoints. Infants followed longitudinally who were stool neutralisation-positive at enrolment had no boost in neutralisation after vaccination, while those stool neutralisation-negative at enrolment experienced a weak boost at 1 month. Stool neutralisation half-life among longitudinal cohort infants was 3.4 months [95% CI 2.6-5.0] for PV1 and 1.7 months [1.4-2.3] for PV3. Moderate evidence suggested concurrent viral intestinal infections were associated with lower neutralisation responses (PV1 p=0.153; PV3 p=0.052). Conclusion: Intestinal antibody responses to poliovirus vaccination were short-lived. The impact of waning intestinal antibodies on transmission risk remains unclear and research is needed to identify vaccination strategies that induce durable mucosal immunity.

This article aims to assess the neurodevelopment of children with and without in utero Zika virus (ZIKV) exposure, in the absence of microcephaly at birth, and to explore social and biological factors associated with develop- mental outcomes. Cross-sectional analysis of 172 children (94 ZIKV-exposed, 78 unexposed), aged 11-39 months, were evaluated using the Bayley Scales of Infant and Toddler Development. . Outcomes were classified as delayed (<70) or at risk (70-84) across cognitive, language, and motor domains. Exposure was confirmed by maternal RT-P- CR or neonatal IgM. Overall, 30.8% of children presented with developmental delay or risk in at least one domain. The most affected domain was language (26.7%). There were no statistically significant differences in delay frequency cognitive and motor domains.

Background: Approximately 1.5 billion doses of novel oral polio vaccine type 2 (nOPV2) have been administered in response to circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks since 2021. Although infants are eligible to receive the vaccine from birth, the induction of intestinal mucosal immunity by nOPV2 in newborns has not been directly evaluated. Methods: In a randomized, placebo-controlled, phase 2 clinical trial in Bangladesh (2020–2021), 215 healthy newborns received 2 doses of either nOPV2 (n = 110) or placebo (sucrose; n = 105), at birth (0–3 days) and 4 weeks later. Intestinal mucosal antibody responses were assessed by measuring poliovirus type 2 (PV2)-specific neutralizing activity and immunoglobulin (Ig)A levels in stool collected biweekly from birth to 8-weeks. Results: Newborns vaccinated with 2 doses of nOPV2 had strong intestinal mucosal antibody responses that differed significantly from the placebo group (P < .0001 for PV2-specific neutralization from 2 weeks onward and P ≤ .007 for PV2-specific IgA from 4 weeks onward). Positive PV2-specific neutralization in stool (titers ≥16) was detected in 51.8% (57/110) of nOPV2-vaccinated newborns at 4 weeks and 90.0% (99/110) at 8 weeks (4 weeks after the second dose). Notably, PV2-specific antibody titers following the second dose were very similar for newborns who did and did not have first dose responses (P = .67 for neutralization and P = .38 for IgA at 8 weeks). Conclusions: Vaccination with 2 doses of nOPV2 in neonates induced strong intestinal mucosal antibody responses. In cVDPV2 outbreak settings, neonatal administration of nOPV2 may be a strategy to enhance population-level intestinal mucosal immunity.

Background: Approximately 1.2 billion doses of novel type 2 oral polio vaccine (nOPV2) have been administered in response to circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks since 2021. Although infants are eligible to receive the vaccine from birth, the induction of intestinal mucosal immunity by nOPV2 in newborns has not been directly evaluated. Methods: In a randomized, placebo-controlled, phase 2 clinical trial in Bangladesh (2020–2021), 215 healthy newborns received two doses of either nOPV2 (n=110) or placebo (sucrose; n=105), at birth (0-3 days) and 4 weeks later. Intestinal mucosal immunity was assessed by measuring poliovirus type 2 (PV2)-specific neutralizing activity and immunoglobulin (Ig)A levels in stool collected biweekly from birth to 8-weeks. Results: Newborns vaccinated with two doses of nOPV2 had strong intestinal mucosal immune responses that differed significantly from the placebo group (pTrial registration number NCT04693286

Background: Although polioviruses (PVs) replicate in lymphoid tissue of both the pharynx and ileum, research on polio vaccine–induced mucosal immunity has predominantly focused on intestinal neutralizing and binding antibody levels measured in stool. Methods: To investigate the extent to which routine immunization with intramuscularly injected inactivated polio vaccine (IPV) may induce nasal and pharyngeal mucosal immunity, we measured PV type-specific neutralization and immunoglobulin (Ig) G, IgA, and IgM levels in nasal secretions, adenoid cell supernatants, and sera collected from 12 children, aged 2–5 years, undergoing planned adenoidectomies. All participants were routinely immunized with IPV and had no known contact with live PVs. Results: PV-specific mucosal neutralization was detected in nasal and adenoid samples, mostly from children who had previously received 4 IPV doses. Across the 3 PV serotypes, both nasal (Spearman ρ ≥ 0.87, P ≤ .0003 for all) and adenoid (Spearman ρ ≥ 0.57, P ≤ .05 for all) neutralization titers correlated with serum neutralization titers. In this small study sample, there was insufficient evidence to determine which Ig isotype(s) was correlated with neutralization. Conclusions: Our findings provide policy-relevant evidence that routine immunization with IPV may induce nasal and pharyngeal mucosal immunity. The observed correlations of nasal and pharyngeal mucosal neutralization with serum neutralization contrast with previous observations of distinct intestinal and serum responses to PV vaccines. Further research is warranted to determine which antibody isotype(s) correlate with polio vaccine–induced nasal and pharyngeal mucosal neutralizing activity and to understand the differences from intestinal mucosal immunity.

Background: The public order and safety (POS) sector remains susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks, as workplace attendance is typically compulsory and close physical contact is often needed. Here, we report on a SARS-CoV-2 outbreak with an attack rate of 39% (9/23), which occurred between 19 and 29 June 2021 among a cohort of new POS recruits participating in a mandatory 18-week training programme in England. Methods: The COVID-OUT (COVID-19 Outbreak investigation to Understand Transmission) study team undertook a multidisciplinary outbreak investigation, including viral surface sampling, workplace environmental assessment, participant viral and antibody testing, and questionnaires, at the two associated training facilities between 5 July and 24 August 2021. Results: Environmental factors, such as ventilation, were deemed inadequate in some areas of the workplace, with carbon dioxide (CO2) levels exceeding 1,500 ppm on multiple occasions within naturally ventilated classrooms. Activities during safety training required close contact, with some necessitating physical contact, physical exertion, and shouting. Furthermore, most participants reported having physical contact with colleagues (67%) and more than one close work contact daily (97%). Conclusions: Our investigation suggests that site- and activity-specific factors likely contributed to the transmission risks within the POS trainee cohort. Potential interventions for mitigating SARS-CoV-2 transmission in this POS training context could include implementing regular rapid lateral flow testing, optimizing natural ventilation, using portable air cleaning devices in classrooms, and expanding use of well-fitted FFP2/FFP3 respirators during activities where prolonged close physical contact is required.