Background: The 17D live-attenuated Yellow Fever Virus (YF) vaccine induces strong protective immunity mediated by both humoral and cellular mechanisms. While neutralizing antibody titres above 10 IU are considered protective, T-cell responses are critical for long-term immunity. The 2014 amendment to WHO guidelines for YF vaccination assume life-long protection following a single 17D dose; however, evidence suggests that immunity may wane in infants routinely vaccinated at 9-12 months, with reduced seroconversion rates reported. Methods: In this sub-study of a Phase 3 trial assessing safety and immunogenicity of a 17D booster in children in The Gambia, we measured YF-specific CD4⁺ and CD8⁺ T-cell responses two to ten years after primary vaccination and at 14 and 28 days following the booster dose. T-cell expression of CD154, TNFα, IL-2, and IFNγ was assessed by flow cytometry following stimulation with vaccine strain 17D or NS4B peptide pools. Ex vivo activation markers HLA-DR and CD38 were also evaluated. Associations between T-cell responses, time since primary vaccination, and antibody titres were explored. Findings: YF-reactive T cells, as measured by at least one marker, were detected in 80% and 55% of children following stimulation with 17D or NS4B peptides respectively, with remaining children lacking detectable cellular immunity. No consistent association was observed between T-cell responses and time since vaccination, except for CD154⁺ CD8⁺ cells, which declined with age. There was a trend for CD154+ T-cell frequencies to be lower in children with highest neutralizing antibody titres, with no other association between cellular immunity and antibody responses detected. Booster vaccination did not enhance YF-specific T-cell responses or increase HLA-DR/CD38 co-expression ex vivo. Interpretation: YF-reactive T cells persist for several years in a high proportion of children following primary 17D vaccination, independent of time since primary dose. A secondary dose does not appear to enhance T-cell responses in children.

Previous research has shown that immune development during the first week of life, i.e. ontogeny, is progressive, consistent and robust, involving large numbers of differentially expressed genes at each sampled time point. To obtain more granular detail about conserved and population-specific ontogeny, the influence of day of life on blood gene expression and cell type composition was examined in two distinct neonatal populations, from The Gambia and Papua New Guinea, employing block randomization strategies to minimize batch effects. This enabled more detailed conclusions about ontogenic program differences between the two cohorts. Population-specific ontogeny revealed mechanistic insights likely to contribute to inherent population-based heterogeneity in the efficiency of neonatal immune responses, including cell cycle, kinesins, and DAP12 signaling in Papua New Guinea, and antigen presentation, clathrin-mediated endocytosis and alpha-defensins in The Gambia. Differences between populations interconnect using protein:protein interaction networks of population-specific genes and pathinkR-based pathway networks and heat maps, thus fitting the concept of pathway/network remodeling. In addition to the population-specific changes, there is a profound core ontogenic gene-expression program involving ~18% of all expressed genes with remarkable 88-96% conservation at each day of life, revealing new contributors to this shared early-life ontogenic program.

BACKGROUND:Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus-diphtheria-acellular pertussis-inactivated poliovirus; Tdap-IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy. METHODS:This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18-40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap-IPV) vaccine or a TT-only vaccine at 28-34 weeks' gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria-tetanus-whole-cell pertussis (DTwP) vaccine or a diphtheria-tetanus-acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-B pertussis IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with ClinicalTrials.gov, NCT03606096. FINDINGS:This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap-IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22-4·59]; p<0·0001) and anti-B pertussis IgG (6·45 [5·94-7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-B pertussis IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79-7·75], p=0·0036 for the TT-DTwP group and 4·40 AU/mL [2·99-6·45], p=0·024 for the Tdap-IPV-DTwP group vs 2·16 AU/mL [1·40-3·32] for the Tdap-IPV-DTaP group). Furthermore, DTaP-vaccinated infants born to mothers who had received the Tdap-IPV vaccine in pregnancy had the lowest anti-B pertussis IgG concentrations, even those who had low concentrations of maternally derived antibodies pre-vaccination. Similarly, compared with TT immunisation, Tdap-IPV immunisation in pregnancy was associated with lower nasal anti-pertussis toxin IgG responses in infants after completion of both DTwP and DTaP primary immunisation series at age 20 weeks, although this blunting was more pronounced after DTwP vaccination (GMC 0·016 international units [IU] per mL [0·011-0·025] for the Tdap-IPV-DTwP group vs 0·073 IU/mL [0·044-0·120] for the TT-DTwP group [p=0·0002] and 0·021 IU/mL [0·014-0·032] for the Tdap-IPV-DTaP group vs 0·058 IU/mL [0·041-0·081] for the TT-DTaP group [p=0·0016]). Broad nasal T-cell-associated cytokine responses were observed after primary vaccination in DTwP-vaccinated but not DTaP-vaccinated infants, with no clear impact of the vaccine given in pregnancy. INTERPRETATION:Tdap-IPV vaccination during pregnancy induces antibodies that are transferred across the placenta to reach the upper airway mucosa of the infant and could contribute to local protection. Although maternally derived antibodies modulate pertussis toxin-specific IgG responses to primary vaccination in the infant, those who received the DTwP vaccine consistently generated higher mucosal IgG to whole-cell B pertussis and showed stronger local cellular activation than those who received the DTaP vaccine, corroborating DTwP-specific mucosal effects identified from animal studies. Taken together, these findings provide mechanistic support for the established early-life protection conferred by immunisation during pregnancy and demonstrate the broader mucosal immunity elicited by DTwP vaccination, informing policy discussions on antenatal vaccination programmes and infant pertussis vaccination schedules. FUNDING:The Innovative Medicines Initiative 2 Joint Undertaking, Horizon 2020, European Federation of Pharmaceutical Industries and Associations, Gates Foundation, Wellcome Trust, and BactiVac.

BACKGROUND:Yellow fever is a vaccine-preventable viral haemorrhagic fever. Vaccine-induced neutralising antibody in children can wane faster than previously thought. This clinical trial investigated the safety and immunogenicity of a yellow fever booster in children of different ages. METHODS:This open-label, non-randomised, single-site, phase 3 vaccine trial conducted at a health centre in The Gambia enrolled healthy children into three cohorts defined by age. The oldest cohort was aged 6-9 years, the middle cohort was aged 4-5 years, and the youngest cohort was aged 1-3 years. Children were eligible if they had received a primary yellow fever vaccine at age 9-12 months and had no history of a serious adverse event to the yellow fever vaccine or immunodeficiency. All children received a yellow fever 17D booster dose. The primary outcome of neutralising antibody responses to the booster was analysed after 28 days using a linear mixed model in children with complete immunology data and who received their primary vaccine in the 9-12-month period. Safety was a coprimary outcome in all participants. There were no missing data. This trial was registered with ClinicalTrials.gov (NCT05332197) and it is complete and closed to new participants. FINDINGS:The trial enrolled 610 children (175 in the oldest cohort, 198 in the middle cohort, and 237 in the youngest cohort) between Sept 6, 2022, and Sept 20, 2023. Median age at booster vaccination was 7·2 years (IQR 6·4-9·7) for the oldest cohort, 4·0 years (3·9-5·2) for the middle cohort, and 2·3 years (1·9-3·4) for the youngest cohort. There was a roughly equal sex split in all three cohorts. Immunology analysis was based on 589 children. Baseline PRNT90 seropositivity occurred in 106 (65% [95% CI 65-72]) of 164 children in the oldest cohort, 130 (67% [60-73]) of 195 children in the middle cohort, and 189 (82% [77-87]) of 230 children in the youngest cohort. 581 (99% [97-99]) of 589 total children were seropositive post-booster. The oldest and middle cohorts had a greater fold change in neutralising antibody on PRNT90 (7·72 [95% CI 6·27-9·16], p=0·0001 for the oldest cohort; and 6·13 [5·08-7·19], p=0·044 for the middle cohort) compared with the youngest cohort (4·62 [3·89-5·35]). There were two severe adverse events; neither were related to the study vaccine. INTERPRETATION:Yellow fever booster vaccination was safe and immunogenic in healthy Gambian children. Protective neutralising antibody waned following primary vaccination and boosting had a more pronounced effect in the oldest and middle cohorts (aged 4-9 years) than in the youngest cohort (aged 1-3 years). These data could be of value to policy makers to inform need and optimal timing of yellow fever booster vaccination in children in endemic areas. FUNDING:Wellcome Trust.

Acute respiratory illnesses (ARIs) in travel medicine clinics pose a particular risk, as they may be the first point of care for returning travelers with respiratory viruses, possibly infecting healthcare workers and leading to further healthcare-associated spread. At the Charité Travel Clinic, a video-based, contactless screening and registration terminal (SRT) was piloted to screen and separate acute patients with an ARI. The primary objective of this study was to determine the accuracy of the SRT in identifying patients with an ARI. The secondary objective was to describe the demographics, symptoms, and travel history of the patients according to their screening classification status. From October 4 to November 22, 2023, 189 unscheduled patients were screened by medical assistants using the audiovisual intercom of the SRT prior to entering the clinic and subsequently received a final diagnosis from a physician. After exclusions, 160 patients were included in the analysis. Screening accuracy was assessed using a confusion matrix comparing SRT screening results with physicians’ final diagnoses. Demographic and symptom data were analyzed by classification status. Among the 160 patients included in the analysis, the median age was 34 years (IQR 28–45.5), and 60% (96/160) were female. ARIs accounted for 14.4% (23/160) of final diagnoses. The SRT demonstrated a sensitivity of 87% (95% CI 66%–97%) and a specificity of 84% (95% CI 77%–90%). The positive predictive value was 48% (95% CI 32%–64%), and the negative predictive value was 97% (95% CI 93%–99%). Cough was the most frequent symptom among true positives (17/20, 85.0%) and the least frequent symptom among false positives (3/22, 13.6%). All three false negative cases were female, reported cough without other ARI symptoms, and were born outside Germany. The SRT was able to reliably rule out ARIs, with a slight tendency to err on the side of caution. In this limited study population, it performed well when compared to algorithm-based digital interventions. Symptom-based, audiovisual screening may help to reduce ARI exposure for healthcare workers and other patients and thus may be a relevant tool for screening in epidemic response.

We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes, and immune cell counts from the EPIC-HIPC newborn cohort, we report that promoter methylation was negatively correlated (Pearson r = −0.5, P < 2.2 × 10−16) with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. Higher promoter methylation at birth was associated with lower UBASH3A expression and reduced early-onset sepsis risk (odds ratio, 0.26; P = .015). Genetic variation significantly influenced variations in baseline UBASH3A methylation (132 cis-meQTL, false discovery rate <0.05).

Objectives Pregnant women are at increased risk of severe illness and adverse pregnancy outcomes during infectious disease outbreaks, yet they are frequently excluded from early emergency vaccine responses. During the COVID-19 pandemic, evolving pregnancy-specific safety evidence contributed to delayed and inconsistent guidance, complicating integration of vaccination into routine maternal health services. This study examined how pregnant women were included in The Gambia’s COVID-19 vaccine rollout and identified priorities to strengthen pregnancy-inclusive preparedness for future emergencies.Design We conducted a qualitative exploratory study in The Gambia using semistructured key informant interviews with healthcare workers and policy influencers followed by facilitator-guided group discussions during a participatory workshop. Data were analysed using a hybrid deductive–inductive framework synthesis approach guided by the Consolidated Framework for Implementation Research (CFIR).Setting The Gambia, within the Ministry of Health facilities and a national workshop venue. Data were collected between September 2023 and November 2024, following national expansion of COVID-19 vaccine eligibility to pregnant women in The Gambia.Participants 15 key informants (healthcare workers and policy influencers involved in maternal health, immunisation and vaccine policy) and 29 participants in a subsequent participatory workshop.Results Across CFIR domains, implementation was shaped by evolving safety and eligibility guidance, which reduced confidence in counselling and contributed to hesitancy. Outer-setting influences included misinformation and social influence within households and communities, alongside trust in ministry of health actors and endorsement by religious and traditional leaders. Inner-setting constraints included fragmented delivery pathways not integrated into antenatal care, transport and cold-chain challenges, and weak documentation and adverse event reporting that limited visible safety reassurance. At the individual level, healthcare workers were trusted but constrained by staffing pressures, long waiting times and limited access to timely information, while visible role-modelling supported acceptance. Suggested strategies included early training, cross-cadre coordination, strengthened logistics and data systems, improved safety monitoring and communication, and investment in workforce retention and sustainable financing.Conclusions Pregnancy-inclusive emergency vaccination requires coordinated action across guidance, community engagement, service organisation, workforce readiness and safety monitoring. Embedding these determinants within routine preparedness, rather than relying on ad hoc emergency responses, can improve equity and effectiveness globally.

Background:Tuberculosis (TB) remains a global health threat, affecting over a million children under the age of 15 annually. Many children with TB do not receive treatment due to challenges in diagnosis. Methods:We performed a multi-omics analysis for pediatric TB by integrating plasma proteomics and metabolomics data from children with presumptive TB across four high-burden countries. Pathway enrichment analysis was conducted using multiGSEA to identify relevant immune and metabolic pathways. We also applied mixOmics and multiview approaches for diagnostic biomarker discovery and compared the performance of multi-omics signatures with those derived from single-omics datasets. Results:Enrichment analysis revealed several immune and metabolic pathways, including PTEN and RUNX2 regulation pathways, as well as arginine and proline metabolism, that were uniquely identified through data integration. While the multi-omics model showed marginal improvement over single-omics models, proteomics alone generally outperformed metabolomics and demonstrated greater potential for accurately classifying Confirmed TB versus Unlikely TB in children. Conclusion:These findings demonstrate the advantage of combining complementary molecular layers to gain a deeper understanding of disease mechanisms and highlight the potential of proteomics for improving pediatric TB diagnosis.

Abstract Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), remains a pressing global health challenge, with a high burden in West Africa, including The Gambia. Understanding the genetic diversity of circulating MTBC strains is essential for improving diagnosis, surveillance and treatment strategies. In this study, we characterise the population structure and drug resistance landscape of MTBC strains circulating in The Gambia over nearly two decades (2002–2021). We analysed whole-genome sequencing (WGS) data from 1,803 TB isolates. Lineage 4 (L4) was predominant (67.2%), followed by the West Africa-restricted lineage 6 (L6, 26.6%), with L4 exhibiting greater genetic diversification over time. Drug susceptibility profiling of these isolates revealed that 78% (1421/1803) were drug-susceptible, while 6.5% (119/1803) harboured resistance to first-line drugs, primarily to isoniazid, rifampicin, or both. Notably, 15.5% (282/1803) isolates carried mutations classified as having uncertain significance according to the WHO resistance catalogue. Comparative analyses revealed a lineage 6-specific ethambutol-associated mutation of uncertain significance (embC Ala307Thr) occurring at a higher frequency in Gambian isolates than in the broader West Africa region or globally. Structural modelling demonstrated that many first-line drug resistance mutations are located in highly conserved, solvent-inaccessible regions of target proteins, often impacting protein stability, suggesting a trade-off between drug resistance, bacterial fitness, and evolutionary adaptation. Together, these findings highlight the coexistence of globally widespread and regionally restricted MTBC lineages in The Gambia and reveal a substantial burden of resistance-associated mutations of uncertain significance in the WHO catalogue. Sustained genomic surveillance and region-specific interpretation of resistance mutations are essential to support End TB strategies in high-burden settings.

OBJECTIVE:To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF). METHODS:MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns. RESULTS:In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy , defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5-93.9) and 70.0% (95% CI, 50.6-82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified. CONCLUSION:This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov , NCT04424316.

Background:Protection of newborns from infection can be achieved through maternal or vaccine-induced antibodies, but the factors influencing vaccine protection (correlate of protection) and subsequent infant immunity remain insufficiently understood. Further investigation is essential to optimize early-life vaccination strategies. Objective:We sought to evaluate the impact of timing and sequence of hepatitis B vaccine (HBV) and Bacille Calmette-Guérin (BCG) vaccine within the first week of life on infant HBV immunogenicity and its relationship with maternal antibodies. Methods:This was an exploratory analysis of a US National Institutes of Health-supported prospective, randomized study of systems biology signatures predictive of HBV immunogenicity in 2 geographically distinct cohorts in The Gambia (GAM; N = 720) and Papua New Guinea (PNG, N = 101) (clinicaltrials.gov NCT03246230). Healthy, hepatitis B surface antigen (anti-HBs)-negative mothers and their infants were enrolled and randomized into 4 vaccine groups: HBV alone, BCG alone, HBV + BCG, or no vaccination (delayed until no later than day of life [DOL]7). Blood samples were collected at birth (DOL0) and on a randomly assigned day (either DOL1, DOL3, or DOL7) with a maximum of 2 blood draws in the first week of life per ethics approval. All infants received catch-up vaccination within DOL7 and the recommended oral polio vaccine within 10 days of birth. Additional blood samples were collected at DOL30 and DOL128 to measure anti-HBs titers and assess immunogenicity. Results:Demographic and clinical characteristics were balanced across vaccine groups, suggesting successful randomization in both cohorts. Similar infant growth trajectories and longitudinal anti-HBs titer trends were observed across all vaccine groups in both cohorts over the first 128 days of life. Maternal and neonatal baseline anti-HBs titers were strongly correlated (GAM: r = 0.98; PNG: r = 0.99). DOL0 titers predicted DOL30 titers (GAM: R 2 = 0.56; PNG: R 2 = 0.945) but not DOL128 titers. Exploratory pairwise comparisons showed that Gambian infants receiving BCG at birth and HBV at DOL7 had higher DOL30 titers than those vaccinated with HBV at DOL1 (Wilcoxon P = .046), whereas in PNG, infants in the HBV + BCG group and the delayed group had higher DOL128 titers than those in the HBV group (Wilcoxon P = .046; Wilcoxon P = .019, respectively). Conclusions:This study demonstrates the feasibility of conducting large-scale neonatal immunogenicity studies in resource-constrained settings. Our observations underscore the importance of vaccine timing and maternal antibodies in shaping early-life vaccine-induced immunogenicity, offering valuable insights for neonatal vaccination schedules.

Abstract Respiratory syncytial virus (RSV) causes over 100,000 annual deaths, predominantly in low- and middle-income countries, yet immunological correlates of protection remain poorly defined in high-burden settings. This study aims to identify immunological correlates of protection against RSV infection, and to compare the relative contribution of systemic and mucosal antibody responses. We use data from an intensively sampled prospective household cohort study in The Gambia, following 342 participants over 12 months with weekly PCR testing and longitudinal serum and nasal sampling. Using a Bayesian hierarchical framework jointly modelling antibody kinetics, household transmission dynamics, and imperfect PCR ascertainment, we characterise humoral immunity to RSV-A antigens across systemic and mucosal compartments. Mucosal IgA to the pre-fusion F (pre-F) protein is the strongest predictor of protection against infection (AUC = 0.72), outperforming serum anti-Pre-F IgG (AUC = 0.66). Serum and mucosal responses are largely compartment-independent (r = 0.02–0.28), with a combined serum and mucosal anti-Pre-F model outperforming either alone, and both biomarkers correlating with RSV-A neutralising titres. These findings have direct implications for designing RSV infection-preventing vaccine strategies.

Pandemic and epidemic intelligence integrates surveillance data with contextual knowledge to assess health risks and inform public health decisions. Although investments in surveillance and public health intelligence have accelerated innovation, research efforts remain thematically and geographically fragmented and the translation of insights into policy and practice is inconsistent. To address this gap, the WHO Hub for Pandemic and Epidemic Intelligence, in collaboration with global partners, conducted a research prioritisation exercise to identify key research gaps and opportunities. Using a structured consultation process and expert-driven scoring, based on a modified Child Health and Nutrition Research Initiative approach, we identified 23 priority research statements across eight thematic domains including data preparedness, quality standards, analytical frameworks, artificial intelligence and technological advances, multisectoral approaches, community-centred approaches, governance, and evidence-to-policy translation. These findings can guide funding agencies, policy makers, and research institutions in prioritising research investments that enhance data integration, diagnostic innovation, and real-time decision making.

Background: Mosquito-borne chikungunya virus (CHIKV) causes acute febrile illness with potentially persisting polyarthralgia, and its global resurgence in international travelers poses a risk of importation into non-endemic regions. Methods: We describe a cluster of ten travelers returning from the Seychelles to Berlin, Germany, between December 2025 and April 2026, diagnosed with acute CHIKV infection at an outpatient travel clinic. The diagnosis was confirmed by either reverse transcription polymerase chain reaction (RT-qPCR) or serological detection of Immunoglobulin M (IgM). Samples with a sufficient viral load were additionally sequenced. Results: Symptomatic patients (six male/four female; age range 27–64 years) presented 1–54 days after symptom onset; most reported fever and arthralgia at disease onset. CHIKV infection was confirmed by PCR in five of seven tested patients and by IgM serology in seven patients, including three PCR-positive cases who were initially seronegative early in infection. No dengue infections were detected. All patients were unvaccinated against CHIKV, and only one had sought pre-travel medical advice. Epidemiological assessment suggested multiple probable exposure sites within the Seychelles. Genomic sequencing was successfully performed in two samples. Conclusions: This cluster reflects ongoing CHIKV activity in the Seychelles and underscores the risk of international spread to Europe. Early diagnostic testing, particularly PCR during the acute phase, is essential to detect potential viremic patients. Improved pre-travel counseling, vaccination uptake, and clinician awareness are needed to reduce missed diagnoses and mitigate the risk of autochthonous transmission in regions with established Aedes mosquito populations.

Sickle cell trait (SCT) is a genetic condition characterized by a heterozygous A-T substitution (Glu to Val) in 1 copy of the β-globin (HBB) gene on chromosome 11. Although often asymptomatic, individuals with SCT can experience complications under stress, such as hypoxia, dehydration, and extreme exertion, leading to vaso-occlusion, organ damage, and impaired immune defenses. Understanding the impact of SCT on the immune system may aid in preventing clinical complications. We genotyped 720 newborns from The Gambia, West Africa, an area in which people are prone to have sickle cell disorders, using RNA-sequencing reads mapped to the HBB gene to identify those with SCT and investigate immune development using single-omics and multiomics approaches. We identified 118 newborns (~17%) with SCT and 4 (0.6%) with sickle cell disease (SCD). Newborns with SCT demonstrated distinct molecular signatures across day of life (DOL) 0, 1, 3, and 7, compared with those without, including reduction of DOL 3 plasma proteins (eg, cysteine-rich secretory protein-3, inter-α-trypsin inhibitor 1, tetranectin, and cadherin-5). Additionally, we observed enrichment of pathways previously associated with SCD, such as the Jison sickle cell pathway, along with those linked to hematologic (chronic leukemia), hepatic (liver cancer), and renal (aging kidney) functions and disorders. These SCT-based associations were validated in an independent cohort of 45 neonates. Despite the absence of overt early clinical phenotypes, SCT-associated changes manifest in the first week of life at the molecular level. Monitoring and characterizing these associations may enable the identification of future disease risks and the development of preventive strategies. This trial was registered at www.clinicaltrials.gov as #NCT03246230.

BACKGROUND Understanding SARS-CoV-2 antibody dynamics is critical for pandemic preparedness, particularly where population immunity has developed through high infection rates with minimal vaccination. Whether predominantly asymptomatic infections confer protective immunity and which biomarkers best predict protection in resource-limited settings remain unclear. METHODS We conducted a household cohort study in The Gambia over 15 months (March 2021-June 2022) during Delta and Omicron waves, with weekly upper respiratory tract sampling for SARS-CoV-2 PCR testing. Serum and mucosal samples were collected at baseline, 6, and 12 months. We measured serum neutralising antibodies and mucosal IgA against five SARS-CoV-2 variants. Using Bayesian hierarchical models, we quantified antibody kinetics and evaluated correlates of protection by predictive accuracy across biomarker-variant combinations. FINDINGS Among 289 participants with 768 serological and mucosal measurements, attack rates of 53% (Delta) and 79% (Omicron) were observed, with 84% of infections asymptomatic. Delta infection produced serum neutralising antibody responses to the Delta variant (27-fold rise at peak, 95% CrI 5.0-95.2) persisting 197 days >4-fold baseline, while Delta mucosal IgA responses were shorter (9-fold rise at peak, 95% CrI 1.7-39.3, persisting 62 days). Delta infections generated substantial cross-reactive boosting to Ancestral and Alpha variants, whereas Omicron boosting was more specific to BA.1. Participants with hybrid immunity from infection and vaccination achieved higher antibody levels (24-fold rise) than those with infection alone (6-fold rise) during the Delta wave. Variant-matched neutralisation demonstrated superior predicted protection performance against infection compared to other biomarkers in both waves (Delta: AUC 0.66; Omicron BA.1: AUC 0.65). INTERPRETATION Predominantly asymptomatic SARS-CoV-2 infections in The Gambia generated robust, durable and protective antibody responses. Variant-matched serum neutralising antibody levels capture protection as effectively as complex multi-biomarker approaches, providing pragmatic guidance for serological surveillance for population immunity in resource-constrained settings. FUNDING United Kingdom Research and Innovation Grant (No. MC\_PC\_19084). ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement. (MC\_PC\_19084). BK and SF are funded by the Einstein Foundation, Berlin ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Study approval was given by the joint Gambia Government and Medical Research Council Unit, The Gambia (MRCG) Ethics committee, and the London School of Hygiene and Tropical Medicine ethics committee (project ID 22556, clinicialtrials.gov [NCT05952336][1]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at https://github.com/ccgh-idd/cop-transvir-sarscov2 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05952336&atom=%2Fmedrxiv%2Fearly%2F2026%2F01%2F04%2F2026.01.02.26343369.atom

Background: Global health emergencies consistently expose and exacerbate vaccine inequities, with high-income countries prioritising their populations and leaving low- and middle-income countries (LMICs) facing delays and shortages. Diseases primarily affecting LMICs receive limited attention from global vaccine developers because of perceived low market value and limited financial return, further entrenching these disparities. Africa’s limited investment in vaccine manufacturing has heightened its vulnerability during outbreaks, including yellow fever, Ebola, meningococcal meningitis, mpox, and most recently, coronavirus disease 2019 (COVID-19). Aim: This study examines the barriers to vaccine equity in Africa and critically analyses Nigeria’s post-COVID-19 efforts to establish a viable, local vaccine manufacturing ecosystem. Setting: The research focuses on Nigeria within the broader African vaccine manufacturing landscape, using it as a case study to explore both national and continental dynamics. Methods: The study draws on document analysis of strategic plans, regulatory reports, and partnership announcements, complemented by qualitative insights from key informant interviews with stakeholders involved in vaccine policy, regulation, and production in Nigeria and across West Africa. Results: Post-pandemic momentum has catalysed significant shifts: Nigeria has developed a national vaccine manufacturing strategy and secured international partnerships and financing commitments. The regulatory authority, National Agency for Food and Drug Administration and Control (NAFDAC), achieved the World Health Organization (WHO) Maturity Level 3 status, marking critical progress. Nonetheless, persistent gaps remain in research and development capacity, workforce development, regulatory agility, and infrastructure readiness. Conclusion: While Nigeria has made notable progress since the COVID-19 pandemic, sustainable vaccine manufacturing requires long-term investment in research and development, policy reform, skills development, and regional cooperation. Failure to address these challenges systematically risks undermining current gains. Contribution: This article provides insights to support ongoing and future investments in Nigeria’s vaccine manufacturing sector, guiding government policy, international partnerships, and potential investors.

Abstract Background A maternal vaccine (MV) and a long-lasting monoclonal antibody (la-mAB) have been licensed to protect children against RSV. Given the swift waning of their protection, we evaluated the added benefit of seasonal la-mAB administration for children born to vaccinated mothers shortly after the RSV season in Germany. Methods We fitted an age- and birth season-structured catalytic model to cross-sectional seroprevalence data of RSV antibodies using a Bayesian framework to estimate the timing of RSV infections in children <5. We then estimated the incidence of severe outcomes in the absence of immunisation in children <1. Finally, we estimated the impact of the MV and of additional la-mAB administration, accounting for the waning of protection. Results We estimate that children would, on average, be 7 months old (mo) at their first infection, those born in the autumn being the youngest at first infection (4 mo). Together with the children born in the winter, they account for 46% of all RSV hospitalisations and 62% of RSV ICU admissions in unimmunised <1 yo. MV would prevent a total of 776 (473-1,122) hospitalisations per 100,000 vaccinees and 73 (51-94) ICU admissions per 100,000 vaccinees, predominantly among autumn-born children. The summer birth cohort would benefit most from additional la-mAB administration, preventing an additional 46% (10-63) of ICU admissions compared to MV alone, corresponding to an additional 25 (4-45) ICU admissions prevented per 100,000 immunised children. Conclusion Compared to MV alone, the impact of MV+la-mAB on RSV hospitalisations and ICU admissions would likely be modest.

Abstract Background Microbiological confirmation of paediatric pulmonary tuberculosis is frequently unattainable, rendering chest radiography a critical yet underutilised diagnostic tool. Methods We conducted a retrospective diagnostic accuracy study of the qXR-version 4.2.1 (Qure.ai), a paediatric-optimized computer-aided detection (CAD) algorithm, for pulmonary tuberculosis. Diagnostic performance was assessed against microbiological (MRS) and clinical reference standards (ClRS). Bayesian latent class analysis (LCA) was applied to address the imperfection of both reference standards in children. Performance was quantified using area under the receiver operating characteristic curve (AUROC) and estimates of sensitivity and specificity. Results We included digital chest radiographs of 932 Gambian children (< 15 years) comprising 80 (9%) children with confirmed tuberculosis, 163 (17%) with unconfirmed tuberculosis, and 689 (74%) classified as unlikely tuberculosis. Against MRS, qXR demonstrated AUROC, sensitivity and specificity of 0.68 (95% CI 0.61–0.75), 54% (95% CI 43–64%), and 82% (95% CI 79–84%), respectively. Against ClRS, the AUROC, sensitivity and specificity were 0.73 (95% CI 0.69–0.77), 41% (95% CI 34–49%), and 87% (95% CI 84–89%), respectively. Bayesian LCA, assuming conditional independence, estimated sensitivity of 79% (95% CrI 65–89%) and specificity of 82% (95% CrI 79–84%). Assuming conditional dependence between qXR and expert radiologist, and between culture and Xpert, estimated sensitivity increased to 89% (95% CrI 71–98%), with specificity remaining at 82% (95% CrI 79–84%). Conclusions Paediatric-optimized qXR algorithm provides a valuable complementary tool for diagnosis of paediatric pulmonary tuberculosis. Conventional reference standards likely underestimate the true diagnostic performance of CAD systems in children.