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Less than 30% of people in Africa received a dose of the COVID-19 vaccine even 18 months after vaccine development 1 . Here, motivated by the observation that residents of remote, rural areas of Sierra Leone faced severe access difficulties 2 , we conducted an intervention with last-mile delivery of doses and health professionals to the most inaccessible areas, along with community mobilization. A cluster randomized controlled trial in 150 communities showed that this intervention with mobile vaccination teams increased the immunization rate by about 26 percentage points within 48–72 h. Moreover, auxiliary populations visited our community vaccination points, which more than doubled the number of inoculations administered. The additional people vaccinated per intervention site translated to an implementation cost of US $33 per person vaccinated. Transportation to reach remote villages accounted for a large share of total intervention costs. Therefore, bundling multiple maternal and child health interventions in the same visit would further reduce costs per person treated. Current research on vaccine delivery maintains a large focus on individual behavioural issues such as hesitancy. Our study demonstrates that prioritizing mobile services to overcome access difficulties faced by remote populations in developing countries can generate increased returns in terms of uptake of health services 3 . A cluster randomized controlled trial in Sierra Leone shows that targeting access to vaccines in remote areas increases uptake, an approach that can be used to improve vaccine equity in developing countries.

Introduction Progress in malaria control has stalled since 2015, highlighting the need for new control tools. The R21/Matrix-M (R21) malaria vaccine, a pre-erythrocytic vaccine recently approved by WHO for small children, may be one of these tools. This trial aims to assess whether seasonal mass vaccination with R21 reduces malaria transmission in The Gambia and Burkina Faso, two countries at the extreme of the transmission spectrum. Methods This is a multi-centre open cluster-randomised controlled trial to assess the impact of mass vaccination with R21 on malaria transmission and morbidity. The trial will be implemented in eastern Gambia (low to moderate transmission) and Central Burkina Faso (intense transmission). Thirty medium-sized villages in The Gambia and 24 in Burkina Faso will be randomised (1:1) to either intervention or control arm. All eligible residents in intervention villages will receive R21 vaccinations in three-monthly rounds, from May to July 2024, prior to the malaria transmission season. A booster vaccine dose will be administered the following year, in June 2025. The primary outcome is malaria prevalence at peak transmission (November 2024). Secondary outcomes include safety and tolerability, incidence of clinical malaria, vaccination coverage and community acceptability, cost and cost-effectiveness of the intervention. Discussion This is the first trial on seasonal mass vaccination aiming at reducing malaria transmission. Strengths of the study include its design as an adequately powered cluster-randomised trial and the inclusion of study sites with differing transmission intensity which will also provide safety and efficacy data for different age groups. Key challenges remain vaccine hesitancy and vaccination coverage. If successful, R21 seasonal mass vaccination will be an innovative intervention to accelerate malaria elimination efforts and reach the goal set in the Global Technical Strategy for malaria 2016–2030. Trial registration Clinical trials.gov, NCT06578572. Registered on 27 March 2024.

Typhoid fever is estimated to affect over 20 million people per year worldwide, with infants, children, and adolescents in south-central and southeast Asia experiencing the greatest burden of disease. The Typhoid Vaccine Acceleration Consortium (TyVAC) aims to support the introduction of typhoid conjugate vaccines into Gavi-eligible countries in an effort to reduce morbidity and mortality from typhoid. TyVAC-Nepal is a large-scale, participant- and observer-blind, individually randomized, controlled trial evaluating the efficacy of a newly developed typhoid conjugate vaccine in an urban setting in Nepal. In order to effectively deliver the trial, a number of key elements required meticulous planning. Public engagement strategies were considered early, and involved the implementation of a tiered approach. Approximately 300 staff were employed and trained in order to achieve the mass vaccination of 20 000 children aged 9 months to ≤16 years old over a 4-month period. There were 19 vaccination clinics established across the Lalitpur metropolitan city in the Kathmandu valley. Participants will be followed for 2 years post-vaccination to measure the rate reduction of blood culture–confirmed typhoid fever in the vaccination arm as compared to the control arm. The experience of conducting this large-scale vaccine trial suggests that comprehensive planning, continuous monitoring, and an ability to adapt plans in response to feedback are key.

Introduction We conducted a community‐randomized trial (NCTBLINDED) in Finland to assess gender‐neutral and girls‐only vaccination strategies with the AS04‐adjuvanted human papillomavirus (HPV)‐16/18 (AS04‐HPV‐16/18)vaccine. Methods Girls and boys (12−15 years) were invited. We randomized 33 communities (1:1:1 ratio): Arm A: 90% of randomly selected girls and boys received AS04‐HPV‐16/18 vaccine and 10% received hepatitis B vaccine (HBV); Arm B: 90% of randomly selected girls received AS04‐HPV‐16/18 vaccine, 10% of girls received HBV, and all boys received HBV; Arm C: all participants received HBV. Effectiveness measurements against prevalence of HPV‐16/18 cervical infection were estimated in girls at 18.5 years. The main measures were: (1) overall effectiveness comparing Arms A or B, regardless of vaccination status, vs Arm C; (2) total effectiveness comparing AS04‐HPV‐16/18 vaccinated girls in pooled Arms A/B vs Arm C; (3) indirect effectiveness (herd effect) comparing girls receiving HBV or unvaccinated in Arm A vs Arm C. Co‐primary objectives were overall effectiveness following gender‐neutral or girls‐only vaccination. Results Of 80,272 adolescents invited, 34,412 were enrolled. Overall effectiveness was 23.8% (95% confidence interval: −19.0, 51.1; P = 0.232) with gender‐neutral vaccination. Following girls‐only vaccination, overall effectiveness was 49.6% (20.1, 68.2; P = 0.004). Total effectiveness was over 90% regardless of vaccination strategy. No herd effect was found. Immunogenicity of the AS04‐HPV‐16/18 vaccine was high in both sexes. Conclusions This study illustrates the difficulty in conducting community randomized trials. It is not plausible that vaccinating boys would reduce overall effectiveness, and the apparent lack of herd effect was unexpected given findings from other studies. This analysis was likely confounded by several factors but confirms the vaccine's high total effectiveness as in clinical trials. This community randomized trial evaluating two HPV vaccination strategies (girls only and gender neutral) in Finland failed to show indirect benefit for girls by vaccinating boys. Several factors might have prevented to show herd effect such as randomization bias. However, the study confirms the high total effectiveness of the vaccine in girls.

Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from −14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs.

Haematology and biochemistry safety monitoring blood results are also reported from the immunology cohort (100 participants with additional visits), at baseline (before the prime dose), at day 28 (before the boost dose) and 7 days post-boost, graded according to a modified US Food and Drug Administration toxicity scale (appendix). In this interim safety analysis, we found an increase in systemic reactogenicity after the boost dose reported by participants in heterologous vaccine schedules in comparison to homologous vaccine schedules, and this was accompanied by increased paracetamol usage. Of note, these data were obtained in participants aged 50 years and older, and reactogenicity might be higher in younger age groups4,5 for whom a mixed vaccination schedule is being advocated in Germany, France, Sweden, Norway, and Denmark among those who have received a ChAd prime dose, in light of concerns regarding thrombotic thrombocytopenia after the first dose of ChAd.6 Pending availability of a more complete safety dataset and immunogenicity results for heterologous prime-boost schedules (to be reported shortly), these data suggest that the two heterologous vaccine schedules in this trial might have some short-term disadvantages.

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al . show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.

The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. National immunization programs offer childhood vaccines through fixed and outreach services within the health system and often, additional supplementary immunization activities (SIAs) are undertaken to fill gaps and boost coverage. Here, we map predicted coverage at 1 × 1 km spatial resolution in five low- and middle-income countries to identify areas that are under-vaccinated via each delivery method using Demographic and Health Surveys data. We compare estimates of the coverage of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTP3), which is typically delivered through routine immunization (RI), with those of measles-containing vaccine (MCV) for which SIAs are also undertaken. We find that SIAs have boosted MCV coverage in some places, but not in others, particularly where RI had been deficient, as depicted by DTP coverage. The modelling approaches outlined here can help to guide geographical prioritization and strategy design. The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. Here, the authors evaluate the relative effectiveness of two major vaccine delivery strategies, namely routine immunization and supplementary immunization activities in five study countries.

The effectiveness of SARS-CoV-2 vaccines in older adults living in long-term care facilities is uncertain. We investigated the protective effect of the first dose of the Oxford-AstraZeneca non-replicating viral-vectored vaccine (ChAdOx1 nCoV-19; AZD1222) and the Pfizer-BioNTech mRNA-based vaccine (BNT162b2) in residents of long-term care facilities in terms of PCR-confirmed SARS-CoV-2 infection over time since vaccination. The VIVALDI study is a prospective cohort study that commenced recruitment on June 11, 2020, to investigate SARS-CoV-2 transmission, infection outcomes, and immunity in residents and staff in long-term care facilities in England that provide residential or nursing care for adults aged 65 years and older. In this cohort study, we included long-term care facility residents undergoing routine asymptomatic SARS-CoV-2 testing between Dec 8, 2020 (the date the vaccine was first deployed in a long-term care facility), and March 15, 2021, using national testing data linked within the COVID-19 Datastore. Using Cox proportional hazards regression, we estimated the relative hazard of PCR-positive infection at 0–6 days, 7–13 days, 14–20 days, 21–27 days, 28–34 days, 35–48 days, and 49 days and beyond after vaccination, comparing unvaccinated and vaccinated person-time from the same cohort of residents, adjusting for age, sex, previous infection, local SARS-CoV-2 incidence, long-term care facility bed capacity, and clustering by long-term care facility. We also compared mean PCR cycle threshold (Ct) values for positive swabs obtained before and after vaccination. The study is registered with ISRCTN, number 14447421. 10 412 care home residents aged 65 years and older from 310 LTCFs were included in this analysis. The median participant age was 86 years (IQR 80–91), 7247 (69·6%) of 10 412 residents were female, and 1155 residents (11·1%) had evidence of previous SARS-CoV-2 infection. 9160 (88·0%) residents received at least one vaccine dose, of whom 6138 (67·0%) received ChAdOx1 and 3022 (33·0%) received BNT162b2. Between Dec 8, 2020, and March 15, 2021, there were 36 352 PCR results in 670 628 person-days, and 1335 PCR-positive infections (713 in unvaccinated residents and 612 in vaccinated residents) were included. Adjusted hazard ratios (HRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days after the first vaccine dose to 0·44 (95% CI 0·24–0·81) at 28–34 days and 0·38 (0·19–0·77) at 35–48 days. Similar effect sizes were seen for ChAdOx1 (adjusted HR 0·32, 95% CI 0·15–0·66) and BNT162b2 (0·35, 0·17–0·71) vaccines at 35–48 days. Mean PCR Ct values were higher for infections that occurred at least 28 days after vaccination than for those occurring before vaccination (31·3 [SD 8·7] in 107 PCR-positive tests vs 26·6 [6·6] in 552 PCR-positive tests; p<0·0001). Single-dose vaccination with BNT162b2 and ChAdOx1 vaccines provides substantial protection against infection in older adults from 4–7 weeks after vaccination and might reduce SARS-CoV-2 transmission. However, the risk of infection is not eliminated, highlighting the ongoing need for non-pharmaceutical interventions to prevent transmission in long-term care facilities. UK Government Department of Health and Social Care.

On Dec 8, 2020, deployment of the first SARS-CoV-2 vaccination authorised for UK use (BNT162b2 mRNA vaccine) began, followed by an adenoviral vector vaccine ChAdOx1 nCoV-19 on Jan 4, 2021. Care home residents and staff, frontline health-care workers, and adults aged 80 years and older were vaccinated first. However, few data exist regarding the effectiveness of these vaccines in older people with many comorbidities. In this post-implementation evaluation of two COVID-19 vaccines, we aimed to determine the effectiveness of one dose in reducing COVID-19-related admissions to hospital in people of advanced age. This prospective test-negative case-control study included adults aged at least 80 years who were admitted to hospital in two NHS trusts in Bristol, UK with signs and symptoms of respiratory disease. Patients who developed symptoms before receiving their vaccine or those who received their vaccine after admission to hospital were excluded, as were those with symptoms that started more than 10 days before hospital admission. We did logistic regression analysis, controlling for time (week), sex, index of multiple deprivations, and care residency status, and sensitivity analyses matched for time and sex using a conditional logistic model adjusting for index of multiple deprivations and care residency status. This study is registered with ISRCTN, number 39557. Between Dec 18, 2020, and Feb 26, 2021, 466 adults were eligible (144 test-positive and 322 test-negative). 18 (13%) of 135 people with SARS-CoV-2 infection and 90 (34%) of 269 controls received one dose of BNT162b2. The adjusted vaccine effectiveness was 71·4% (95% CI 46·5–90·6). Nine (25%) of 36 people with COVID-19 infection and 53 (59%) of 90 controls received one dose of ChAdOx1 nCoV-19. The adjusted vaccine effectiveness was 80·4% (95% CI 36·4–94·5). When BNT162b2 effectiveness analysis was restricted to the period covered by ChAdOx1 nCoV-19, the estimate was 79·3% (95% CI 47·0–92·5). One dose of either BNT162b2 or ChAdOx1 nCoV-19 resulted in substantial risk reductions of COVID-19-related hospitalisation in people aged at least 80 years. Pfizer.