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Abstract: The Sunshine Coast Public Health Unit (SCPHU) identified a measles case in a childcare educator (CE) with secondary vaccine failure (SVF). The CE had been exposed to a confirmed measles case in a hospital emergency department and later developed symptoms including fever, cough, malaise, and a rash. Diagnostic tests confirmed measles virus infection. Sunshine Coast Public Health Unit (SCPHU) implemented control measures including contact tracing, vaccination, post-exposure prophylaxis, and quarantine for susceptible contacts. Out of 372 identified contacts, 72 were identified as susceptible, all of whom were infants and children. Despite the CE having close contact to all susceptible infants and children, no onward transmission occurred. This suggests that SVF cases pose a lower risk of spreading measles compared to immunologically naïve individuals. This report highlights the importance of prioritising immunologically naïve cases in outbreak responses., (© Commonwealth of Australia CC BY-NC-ND.)

The persistence of measles in many countries demonstrates large immunity gaps, resulting from incomplete or ineffective immunization with measles-containing vaccines (MCVs). MCV impact is determined, in part, by vaccination age. Infants who receive dose 1 (MCV1) at older ages have a reduced risk of vaccine failure, but also an increased risk of contracting infection before vaccination. Here, we designed a new method-based on a mathematical transmission model incorporating realistic vaccination delays and age variations in MCV1 effectiveness-to capture the MCV1 age risk trade-off and estimate the optimal age for recommending MCV1. We applied this method to a range of synthetic populations representing lower- and higher-income populations. We predict a large heterogeneity in the optimal MCV1 ages (range: 6-20 months), contrasting the homogeneity of observed recommendations worldwide. Furthermore, we show that the optimal age depends on the local epidemiology of measles, with a lower optimal age predicted in populations having lower vaccination coverage or suffering higher transmission. Overall, our results suggest the scope for public health authorities to tailor the recommended schedule for better measles control., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

On April 24, 2023, the American Samoa Department of Health (ASDoH) declared a public health emergency amid concern about a possible measles outbreak given low 2-dose vaccination coverage at the time. ASDoH had received two positive measles immunoglobulin (Ig) M test results after Flag Day festivities 1 week earlier from vaccinated children. ASDoH performed active case finding, took actions to mitigate transmission, and requested technical assistance from CDC. ASDoH implemented a vaccination campaign to improve suboptimal coverage. Confirmatory molecular testing of specimens from these initial persons under investigation (PUIs) was not possible, but subsequent testing of specimens from additional PUIs by Hawaii State Laboratories Division and CDC ruled out measles. In settings with low measles prevalence, measles antibody testing results have low positive predictive value and can lead to difficulties with interpreting results. Testing for additional pathogens revealed a variety of viruses known to cause common childhood viral exanthems. Both molecular and serologic testing should be performed for all suspected measles cases. To decrease the probability of false-positive IgM results, testing should be reserved for cases that meet the Council of State and Territorial Epidemiologists measles case definition, especially those in persons with no evidence of immunity and with a history of recent international travel. In addition, maintaining high measles vaccination coverage can prevent future outbreaks., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Annette Fa’alevao Ilimaleota reports travel support from the Pacific Island Health Officers Association and the World Health Organization and an uncompensated leadership role in the U.S.-Affiliated Pacific Islands Serology Technicians Program Collaboration and Service Integration as the Coordinator for American Samoa. No other potential conflicts of interest were disclosed.

Background: The global initiative to eliminate measles, spearheaded by the World Health Organization, has yet to achieve its intended goals. In Turkey, despite robust vaccination strategies, recent increases in measles cases have been attributed to vaccine hesitancy and irregular migration. This study evaluates measles serology within a pediatric population to determine the impact of vaccination regimens on immunity., Methods: A retrospective study at Ankara Bilkent City Hospital analyzed serum measles IgG levels in children aged 1-18 years from January 2020 to August 2023. Exclusions were applied for individuals with positive IgM results, incomplete vaccinations, and immunocompromised conditions. Patients were categorized based on their M-M-R ® II vaccine status into those having received either one or two doses. Seropositivity was assessed using the ELISA method., Results: Of the 686 children, 30.2% received a single dose, and 69.8% received two doses of the MMR vaccine. Overall, 70.7% exhibited positive IgG levels. No significant differences were found in IgG levels between those who received one dose and those who received two doses. However, a decline in IgG levels was observed with age, particularly notable in adolescents aged 14-18 years., Conclusion: The study reveals seropositivity rates lower than expected, highlighting challenges in achieving WHO targets. This suggests a potential need for booster doses during adolescence to maintain protective antibody levels. The findings emphasize the importance of continued surveillance and research to adapt vaccination strategies effectively and prevent measles outbreaks, particularly considering the decline in antibody levels and diverse vaccination histories across populations., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical standards of the institutional and national research committees, and with the 1975 Helsinki Declaration and its later amendments. Ethical approval was granted by the Ethics Committee of Ankara Bilkent City Hospital. Where applicable, general consent for the use of medical records in research was obtained as part of the admission process. Consent for publication No interventions were performed on any patients for the purposes of this study; only existing medical records were utilized. Data was anonymized and confidentiality was maintained in compliance with ethical standards. The information used was in accordance with the general consent provided by patients at the time of their admission to the hospital. Competing interests The authors declare no competing interests. Clinical trial registration This study does not involve any clinical trials. Therefore, no clinical trial registration is required., (© 2024. The Author(s).)

Background: Vaccinating pediatric solid organ transplant candidates against measles and varicella is crucial due to the risk of severe disease in immunosuppressed recipients and general avoidance of live virus vaccines post-transplantation. The world saw a resurgence of measles starting 2012 prompting the American Society of Transplantation in 2015 to release guidelines on recognition, prevention, and post-exposure prophylaxis of this disease in solid transplant recipients. This study aims to assess the extent of incomplete immunity to these viruses in candidates and the approach to immunity optimization during a period of heightened awareness., Methods: A cross-sectional study from 2012 to 2016 at Cleveland Clinic Children's included pediatric solid organ transplant candidates. Data on vaccination history, serology, and demographics were collected. Incomplete immunity was defined by incomplete vaccination or seronegativity., Results: Among 91 candidates, 54.9% had complete varicella vaccination. Serological varicella immunity among patients tested varied by age: < 7 years, 50.0% positive in patients with complete schedules, none in the incomplete; ≥ 7 years, 50.0% positive in patients with complete schedules, 65.5% in the incomplete. For measles, 69.2% had complete vaccination, with immunity varying by age among those tested: < 7 years, 84.6% positive in patients with complete schedules, 42.9% in the incomplete; ≥ 7 years, 81.0% with complete, 62.5% with incomplete. Only 31.1% of those who qualified for a varicella additional dose and 28% who qualified for an additional measles dose received it, respectively., Conclusions: Incomplete immunity to varicella and measles was prevalent in pediatric solid organ transplant candidates at our center during the study period. Despite an increase in global measles activity, our efforts to optimize immunity through additional vaccine doses were only partially successful. Future research should focus on addressing strategies and understanding barriers to ensure timely vaccination for this vulnerable population prior to transplant, especially during periods of increased viral activity., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Objectives: Between 2003 and 2019, three trials (randomised controlled trials [RCTs]) in Guinea-Bissau randomised infants to an early 2-dose measles vaccine (MV) schedule at 4 and 9 months vs standard MV at 9 months. The RCTs produced contradictory mortality results; the effect being beneficial in the 2-dose group in the first but tending to have higher mortality in the last two RCTs. We hypothesised that increased frequency of campaigns with oral polio vaccine (C-OPV) explained the pattern., Methods: We performed per-protocol analysis of individual-level survival data from the three RCTs in Cox proportional hazards models yielding hazard ratios (HR) for the 2-dose vs the 1-dose MV group. We examined whether timing of C-OPVs and early administration of OPV0 (birth to day 14) affected the HRs for 2-dose/1-dose MV., Results: The combined HR(2-dose/1-dose) was 0.79 (95% confidence interval: 0.62-1.00) for children receiving no C-OPV-before-enrolment, but 1.39 (0.97-1.99) for those receiving C-OPV-before-enrolment (homogeneity, P = 0.01). C-OPV-before-enrolment had a beneficial effect in the 1-dose group but tended to have a negative effect in the 2-dose group, especially in females. These effects were amplified further by early administration of OPV0., Conclusion: In the absence of C-OPVs, an early 2-dose MV strategy had beneficial effects on mortality, but frequent C-OPVs may have benefitted the 1-dose group more than the 2-dose MV group, leading to varying results depending on the intensity of C-OPVs., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Measles vaccination has greatly reduced the disease burden worldwide, but challenges remain due to variations in vaccine effectiveness across age groups. This study aimed to assess the serological profile of measles antibodies across different age groups, evaluate the impact of maternal immunity on antibody levels in infants under 12 months, and assess measles immunity in vaccinated individuals., Material and Methods: This cross-sectional study was conducted from June 2022 to January 2023 at the Children's Medical Center, a referral hospital in Iran. Serum samples were tested for measles-specific IgG and IgM antibodies using a commercial enzyme-linked immunosorbent assay (ELSA). An avidity assay was performed to assess measles virus-specific IgG antibodies on the samples that were positive and borderline for the measles IgG ELISA., Results: The study included 969 participants across various age groups. Among them, 23% (221 out of 953) tested positive for measles IgM ELISA, and 52% (504 out of 969) for measles IgG ELISA. Regarding the avidity assay for measles virus-specific IgG, the majority (418 out of 573, 73%) showed high-avidity antibodies. Measles-specific IgG levels varied significantly across different age groups, with infants below 6 months old showing a mean IgG level of 477 mIU/mL, declining to 230 mIU/mL between 6 and 12 months, and increasing significantly to 683 mIU/mL in the 12 to 18 month age group, reaching a peak at 938 mIU/mL among children aged 18-72 months., Conclusion: The increasing IgM positivity among young Iranians suggests a rising risk of measles outbreaks, possibly due to vaccination gaps. Inadequate antibody levels in infants raise concerns about vaccination effectiveness. Considering declining maternal antibodies, vaccinating infants at 6-9 months could be beneficial. Boosters for adolescents and women may further mitigate outbreak risks., Competing Interests: Declaration of competing interest The authors declared no conflicts of interest in connection with the research, authorship, and/or publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Isolation of cases and quarantining of non-immune contacts are the mainstay of measles outbreak management in elimination settings. Serology testing of exposed contacts may not be feasible in large outbreaks; therefore, vaccination history is used as a proxy for determining immunity to measles and thus prevention of onward virus transmission. This study sought to investigate the risk of measles virus transmission from individuals with a history of one or two doses of measles-containing vaccine (MCV)., Methods:  Retrospective analysis of data from measles cases reported to Auckland Regional Public Health Service during the 2019 Auckland region measles outbreak. Vaccination history was verified using patient records and the New Zealand National Immunisation Register. Onward transmission was determined through case interviews and assessment of exposed contacts., Results:  1451 measles cases were assessed as eligible for vaccination at the time of measles outbreak. Of these, 1015 (70.0%) were unvaccinated, 220 (15.2%) had unknown vaccination status, 139 (9.6%) had received only one dose of MCV and 77 (5.3%) had received two doses of the vaccine. Compared to unvaccinated cases, the odds of onward transmission were lower among those with one dose only (OR 0.41, 95% CI: 0.20-0.75) or two doses of MCV (OR 0.44, 95% CI: 0.17-0.95). Median time since vaccination was longer among those with onward transmission compared to those without onward transmission for one and two doses of the vaccine, suggesting a potential effect of waning immunity among this cohort., Conclusion:  These findings support the hypothesis that measles cases with a history of prior vaccination are less likely to transmit the virus to others compared to unvaccinated cases. Such information can be used to support decisions around quarantine requirements for vaccinated contacts in future measles outbreaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors attest they meet the ICMJE criteria for authorship., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Among people infected with measles in England between 2010 and 2019, the proportion of cases who had previously received two doses of vaccine has increased, especially among young adults. Possible explanations include rare infections in vaccinated individuals who did not gain immunity upon vaccination, made more common because fewer individuals in the population were born in the endemic era, before vaccination was introduced, and exposed as part of endemic transmission, or the waning of vaccine-induced immunity, which would present new challenges for measles control in near-elimination settings. We aimed to evaluate whether measles dynamics observed in England between 2010 and 2019 were in line with a waning of vaccine-induced immunity., Methods: We used a compartmental mathematical model stratified by age group, region, and vaccine status, fitted to individual-level case data reported in England from 2010 to 2019 and collected by the UK Health Security Agency. The deterministic model was fitted using Monte Carlo Markov Chains under three scenarios: without the waning of vaccine-induced immunity, with waning depending on time since vaccination, and with waning depending on time since vaccination, starting in 2000. We generated stochastic simulations from the fitted parameter sets to evaluate which scenarios could replicate the transmission dynamics observed in vaccinated cases in England., Findings: The scenario without waning overestimated the number of one-dose recipients among measles cases, and underestimated the number of two-dose recipients among cases older than 15 years (median 75 cases [95% simulation interval (SI) 44-124] in simulations without waning, 196 [95% SI 122-315] in simulations when waning was included, 188 [95% SI 118-301] in simulations when waning started in 2000, and 202 observed cases). The number of onward transmissions from vaccinated cases was 83% (95% credible interval 72-91%) of the number of transmissions from unvaccinated cases. The estimated waning rate was slow (0·039% per year of age; 95% credible interval 0·034-0·044% per year in the best-fitting scenario with waning starting in 2000), but sufficient to increase measles burden., Interpretation: Measles case dynamics in England are consistent with scenarios assuming the waning of vaccine-induced immunity. Since measles is highly infectious, slow waning leads to a heightened burden in outbreaks, increasing the number of measles cases in people who are both vaccinated and unvaccinated. Our findings show that although the vaccine remains highly protective against measles infections for decades and most transmission is connected to people who are unvaccinated, breakthrough infections are increasingly frequent for individuals aged 15 years and older who have been vaccinated twice., Funding: National Institute for Health and Care Research and Wellcome Trust., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Measles is a highly transmissible systemic viral infection associated with substantial mortality primarily due to secondary infections. Measles induces lifelong immunity to reinfection but loss of immunity to other pathogens. An attenuated live virus vaccine is highly effective, but lapses in delivery have resulted in increasing cases worldwide. Although the primary cause of failure to control measles is failure to vaccinate, waning vaccine-induced immunity and the possible emergence of more virulent virus strains may also contribute., Competing Interests: The authors declare no conflict of interest

Although neutralizing antibody is an established correlate of protection for measles, T cell-mediated responses play at least two critical roles in immunity to measles: first, through provision of 'help' enabling robust humoral immune responses; and second, through clearance of measles virus-infected cells. Previously, we identified 13 measles-derived peptides that bound to human leukocyte antigen (HLA) molecules in Priess cells infected with measles virus. In this study, we evaluated the immunogenicity of these peptides in a transgenic mouse model. Our results demonstrated that these peptides induced Th1-biased immune responses at varying levels. Of the 13 peptides, the top four immunogenic peptides were further selected for a viral challenge study in mice. A vaccine based on a combination of these four peptides reduced morbidity and weight loss after viral challenge compared to placebo. Our results emphasize the potential of T cell-mediated, peptide-based vaccines against measles., (© 2024. The Author(s).)

Background and Objectives: In a highly vaccinated population, an increasing number of previously vaccinated measles cases can be expected. The aim of this study was to assess the effect of vaccination on the clinical course and immune response in relation to the current measles case definition., Methods: The presence of fever, catarrhal symptoms, exanthema and complications, and specific IgM and IgG positivity were assessed in all 230 patients and compared in 193 patients with known vaccination status, divided into measles-containing vaccine (MCV) groups: MCV0 (85 patients), MCV1 (25 patients) and MCV2 (83 patients)., Results: Statistically significant differences between groups were found for catarrhal symptoms. Conjunctivitis and rhinitis were significantly less frequent in the MCV2 group (47% and 54%) compared to MCV0 (80% and 80%), p  < 0.001 and p  = 0.002 respectively. Typical exanthema was present in 74 (87%) MCV0 and 56 (67%) MCV2 patients, p  = 0.005. Complications were most common in the MCV0 group (29%). ECDC clinical case criteria were met in 81 (95%) MCV0, 18 (72%) MCV1 and 59 (71%) MCV2 patients, p  < 0.001. IgM were positive in 64 (83%) MCV0, 14 (74%) MCV1 and 36 (67%) MCV2 patients, differences were not statistically significant. There were highly significant differences in IgG between MCV0 and both vaccinated groups ( p  < 0.001)., Conclusions: A redefinition of the clinical case classification is essential to better capture modified measles and to raise awareness among healthcare workers of the differences in measles in vaccinated patients.

The seropositivity of measles antibodies among 261 autologous stem cell transplant recipients (ASCTs) in Korea, assessed approximately 1-2 years after transplant (median, 11 months; interquartile range, 9-14), was significantly lower than age- and sex-matched control healthcare workers (83.1% [217/261] vs. 90.3% [539/597], P = 0.002). The findings underscore the vulnerability of adult ASCT recipients to measles. Clinicians should prioritize testing for measles IgG after ASCT and consider vaccination for ASCT recipients who remain seronegative 2 years after ASCT., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Competing Interests: AH, VH, SH, PK, SD, and AR were responsible for the original design and preparation of this Correspondence. AS and NP collated and analysed the secondary immunodeficiency cohort measles and clinical data and contributed to the writing of the Correspondence and figures and table preparation. SF was responsible for the measles testing of the COCO cohort, analysis of birth groups, and figure and table preparation. OG was responsible for the measles testing of the VIBRANT cohort, analysis, and contributed to writing of the Correspondence. AS and AR have accessed and verified all underlying data. All authors had full access to the data in the Correspondence and had final responsibility for the decision to submit for publication. We declare no competing interests related to this Correspondence. AH has received unrelated grant funding from Wellcome Trust, Medical Research Council (MRC), British Society for Antimicrobial Chemotherapy, and Medical Research Foundation. AH acts as a clinical consultant for the WHO Global Influenza Programme, Department of Health and Social Care Scientific Advisory Group for Serology Testing, National Institute for Clinical Excellence, and Scotland Medicines consortium; and is a data monitoring committee member for the BALANCE trial (NCT03005145). AR has received unrelated grant funding from UK Research and Innovation (UKRI) and MRC. SD has received unrelated grant funding from MRC, UKRI, National Institute for Health and Care Research, and Wellcome Trust. VH has received unrelated grant funding from MRC and Health Data Research UK, and is supported by the UK Health Security Agency and the UK Department of Health. The authors welcome applications from researchers looking to use the data published herein. Applications should be directed to the corresponding author and will be reviewed by the authorship group and subject to the establishment of data sharing agreements. This work is a compilation from three different studies and four different funding sources where data on measles immunity has been tested as part of the study and then combined to provide the narrative in this Correspondence. The COCO study was funded by the UK Medical Research Council. The VIBRANT and SIREN studies were funded by UK Research & Innovation COVID-19 Rapid Response Initiative. Laboratory validation and verification of the measles ELISAs was supported by funding from the UK Medical Research Council (MX/X502996/1). Relevant Ethics committee approvals were from Camden and Kings Cross Research Ethics Committee (20/HRA/1817) for the COCO study and the Chelsea Research Ethics Committee (21/HRA/5433) for the VIBRANT study.

Measles remains a major threat to human health despite widespread vaccination. While we know that maternal antibodies can impair vaccine-induced immunity, the relative contributions of pre-existing immunity levels, maternal and infant characteristics on vaccine responses remain unclear, hampering evidence-based vaccination policy development. Here we combine serological data from 1,505 individuals (aged 0-12 years) in a mother-infant cohort and in a child cohort with empirical models to reconstruct antibody trajectories from birth. We show that while highly heterogeneous across a population, measles antibody evolution is strongly predictive from birth at the individual level, including following vaccination. Further, we find that caesarean section births were linked with 2.56 (95% confidence interval: 1.06-6.37) increased odds of primary vaccine failure, highlighting the long-term immunological consequences of birth route. Finally, we use our new understanding of antibody evolution to critically assess the population-level consequences of different vaccination schedules, the results of which will allow country-level evaluations of vaccine policy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Vietnam continues to have measles and rubella outbreaks following supplementary immunization activities (SIA) and routine immunization despite both having high reported coverage. To evaluate immunization activities, age-specific immunity against measles and rubella, and the number of averted Congenital Rubella Syndrome (CRS) cases, must be estimated., Methods: Dried blood spots were collected from 2091 randomly selected individuals aged 1-39 years. Measles and rubella virus-specific immunoglobulin G (IgG) were measured by enzyme immunoassay. Results were considered positive at ≥120 mIU/mL for measles and ≥10 IU/mL for rubella. The number of CRS cases averted by immunization since 2014 were estimated using mathematical modelling., Results: Overall IgG seroprevalence was 99.7% (95%CI: 99.2-99.9) for measles and 83.6% (95%CI: 79.3-87.1) for rubella. Rubella IgG seroprevalence was higher among age groups targeted in the SIA than in non-targeted young adults (95.4% [95%CI: 92.9-97.0] vs 72.4% [95%CI: 63.1-80.1]; P < 0.001). The estimated number of CRS cases averted in 2019 by immunization activities since 2014 ranged from 126 (95%CI: 0-460) to 883 (95%CI: 0-2271) depending on the assumed postvaccination reduction in the force of infection., Conclusions: The results suggest the SIA was effective, while young adults born before 1998 who remain unprotected for rubella require further vaccination., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Measles has been a significant public health concern in Pakistan, especially in the Khyber Pakhtunkhwa (KPK) province, where sporadic and silent epidemics continue to challenge existing control measures. This study aimed to estimate the prevalence and investigate the molecular epidemiology of the measles virus (MeV) in KPK and explore the vaccination status among the suspected individuals., Methods: A cross-sectional study was conducted between February and October 2021. A total of 336 suspected measles cases from the study population were analyzed for IgM antibodies using Enzyme-Linked Immunosorbent Assay (ELISA). Throat swabs were randomly collected from a subset of positive cases for molecular analysis. Phylogenetic analysis of MeV isolates was performed using the neighbor-joining method. The vaccination status of individuals was also recorded., Results: Among the suspected participants, 61.0% (205/336) were ELISA positive for IgM antibodies, with a higher prevalence in males (64.17%) compared to females (57.04%). The majority of cases (36.0%) were observed in infants and toddlers, consistent with previous reports. The majority of IgM-positive cases (71.7%) had not received any dose of measles vaccine, highlighting gaps in vaccine coverage and the need for improved immunization programs. Genetic analysis revealed that all MeV isolates belonged to the B3 genotype, with minor genetic variations from previously reported variants in the region., Conclusion: This study provides valuable insights into the genetic epidemiology of the MeV in KPK, Pakistan. The high incidence of measles infection among unvaccinated individuals highlights the urgency of raising awareness about vaccine importance and strengthening routine immunization programs., Competing Interests: Declaration of Competing Interest All authors have read the manuscript and declare no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: We explored the role of metabolic hormones and the B-cell repertoire in the association between nutritional status and vaccine responses., Methods: In this prospective cohort study, nested within a larger randomized open-label trial, 211 South African children received two doses of measles vaccine and two or three doses of pneumococcal conjugate vaccine (PCV). Metabolic markers (leptin, ghrelin and adiponectin) and distribution of B-cell subsets (n = 106) were assessed at 18 months of age., Results: Children with a weight-for-height z-score (WHZ) ≤ -1 standard deviation (SD) at booster vaccination had a decreased mean serotype-specific PCV IgG response compared with those with WHZ > -1 and <+1 SD or WHZ ≥ +1 SD at 9 months post-booster (18 months of age). (Naive) pre-germinal center B-cells were associated with pneumococcal antibody decay between one to nine months post-booster. Predictive performance of elastic net models for the combined effect of B-cell subsets, metabolic hormones and nutritional status (in addition to age, sex, and randomization group) on measles and PCV vaccine response had an average area under the receiver operating curve of 0.9 and 0.7, respectively., Conclusions: The combined effect of B-cell subsets, metabolic hormones and nutritional status correlated well with the vaccination response for measles and most PCV serotypes., Clinicaltrials: gov registration of parent studies: NCT02943902 and NCT03330171., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Countries with moderate to high measles-containing vaccine coverage face challenges in reaching the remaining measles zero-dose children. There is growing interest in targeted vaccination activities to reach these children. We developed a framework for prioritizing districts for targeted measles and rubella supplementary immunization activities (SIAs) for Zambia in 2020, incorporating the use of the WHO's Measles Risk Assessment Tool (MRAT) and serosurveys. This framework was used to build a model comparing the cost of vaccinating one zero-dose child under three vaccination scenarios: standard nationwide SIA, targeted subnational SIA informed by MRAT, and targeted subnational SIA informed by both MRAT and measles seroprevalence data. In the last scenario, measles seroprevalence data are acquired via either a community-based serosurvey, residual blood samples from health facilities, or community-based IgG point-of-contact rapid diagnostic testing. The deterministic model found that the standard nationwide SIA is the least cost-efficient strategy at 13.75 USD per zero-dose child vaccinated. Targeted SIA informed by MRAT was the most cost-efficient at 7.63 USD per zero-dose child, assuming that routine immunization is just as effective as subnational SIA in reaching zero-dose children. Under similar conditions, a targeted subnational SIA informed by both MRAT and seroprevalence data resulted in 8.17-8.35 USD per zero-dose child vaccinated, suggesting that use of seroprevalence to inform SIA planning may not be as cost prohibitive as previously thought. Further refinement to the decision framework incorporating additional data may yield strategies to better target the zero-dose population in a financially feasible manner.

In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice. After single immunization, V591 induced similar neutralization titers as observed in sera of convalescent patients. The cellular immune response was confirmed to be Th1 skewed. V591 conferred long-lasting protection against SARS-CoV-2 challenge in a murine model with marked decrease in viral RNA load, absence of detectable infectious virus loads, and reduced lesions in the lungs. V591 was furthermore efficacious in an established non-human primate model of disease (see companion article [S. Nambulli, N. Escriou, L. J. Rennick, M. J. Demers, N. L. Tilston-Lunel et al., J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23]). Thus, V591 was taken forward into phase I/II clinical trials in August 2020. Unexpected low immunogenicity in humans (O. Launay, C. Artaud, M. Lachâtre, M. Ait-Ahmed, J. Klein et al., eBioMedicine 75:103810, 2022, https://doi.org/10.1016/j.ebiom.2021.103810) revealed that the underlying mechanisms for resistance or sensitivity to pre-existing anti-measles immunity are not yet understood. Different hypotheses are discussed here, which will be important to investigate for further development of the measles-vectored vaccine platform.IMPORTANCESARS-CoV-2 emerged at the end of 2019 and rapidly spread worldwide causing the COVID-19 pandemic that urgently called for vaccines. We developed a vaccine candidate using the highly efficacious measles vaccine as vector, a technology which has proved highly promising in clinical trials for other pathogens. We report here and in the companion article by Nambulli et al. (J Virol 98:e01762-23, 2024, https://doi.org/10.1128/jvi.01762-23) the design, selection, and preclinical efficacy of the V591 vaccine candidate that was moved into clinical development in August 2020, 7 months after the identification of SARS-CoV-2 in Wuhan. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform., Competing Interests: J. Brunet, Z.C., M.G., H.S.-M., M.M., P.C., L. Majlessi, C.G., A.M., and N.E. are inventors of a patent application describing measles-vectored vaccine candidates against SARS-CoV-2. All other authors declare no financial or non-financial competing interests.

Background: Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children., Methods: This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18-40 years for the adult cohort, 15-18 months for toddlers, or 9-10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete., Findings: Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0-97·2) seroconverted to measles and 100% (58/58; 93·8-100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2-95·2) and 100% (59/59; 93·9-100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events., Interpretation: The safety and immunogenicity data support the accelerated development of the MRV-MNP., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests SH, DVM, MRP, and MR are employees of, or affiliated with, Micron Biomedical. All other authors declare no competing interests. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine diagnoses. We performed rRT-PCR and measles-specific IgM testing on samples from 541 suspected measles cases. Of the 24 IgM-positive and rRT-PCR--negative cases, 20 were among children who received a measles-containing vaccine within the previous 6 months; most had low IgG relative avidity indexes (RAIs). The other 4 cases were among adults who had an unknown previous measles history, unknown vaccination status, and high RAIs. We detected viral nucleic acid for viruses other than measles in 15 (62.5%) of the 24 cases with discrepant rRT-PCR and IgM test results. Measles vaccination, measles history, and contact history should be considered in suspected measles cases with discrepant rRT-PCR and IgM test results. If in doubt, measles IgG avidity and PCR testing for other febrile exanthematous viruses can help confirm or refute the diagnosis.

Several COVID-19 vaccines have now been deployed to tackle the SARS-CoV-2 pandemic, most of them based on messenger RNA or adenovirus vectors.The duration of protection afforded by these vaccines is unknown, as well as their capacity to protect from emerging new variants. To provide sufficient coverage for the world population, additional strategies need to be tested. The live pediatric measles vaccine (MV) is an attractive approach, given its extensive safety and efficacy history, along with its established large-scale manufacturing capacity. We develop an MV-based SARS-CoV-2 vaccine expressing the prefusion-stabilized, membrane-anchored full-length S antigen, which proves to be efficient at eliciting strong Th1-dominant T-cell responses and high neutralizing antibody titers. In both mouse and golden Syrian hamster models, these responses protect the animals from intranasal infectious challenge. Additionally, the elicited antibodies efficiently neutralize in vitro the three currently circulating variants of SARS-CoV-2., (© 2021. The Author(s).)

The MMR vaccination program was introduced in Spain in 1981. Consistently high vaccination coverage has led to Spain being declared free of endemic measles transmission since 2014. A few imported and import-related cases were reported during the post-elimination phase (2014 to 2020), with very low incidence: three cases per million of inhabitants a year, 70% in adults. In the post-elimination phase an increasing proportion of measles appeared in two-dose vaccinated individuals (up to 14%), posing a challenge to surveillance and laboratory investigations. Severity and clinical presentation were milder among the vaccinated. The IgM response varied and the viral load decreased, making the virus more difficult to detect. A valid set of samples (serum, urine and throat swab) is strongly recommended for accurate case classification. One third of measles in fully vaccinated people was contracted in healthcare settings, mainly in doctors and nurses, consistent with the important role of high intensity exposure in measles breakthrough cases. Surveillance protocols and laboratory algorithms should be adapted in advanced elimination settings. Reinforcing the immunity of people working in high exposure environments, such as healthcare settings, and implementing additional infection control measures, such as masking and social distancing, are becoming crucial for the global aim of measles eradication.

Background: The relationship between allergic individuals and their responsiveness to routine vaccines has rarely been investigated. This study examined whether the seroprevalence of measles antibody differed between children with and without allergic diseases in the general pediatric population., Methods: The cross-sectional study was performed within a prospective general birth cohort (a pilot study of the Japan Environment & Children's Pilot Study [JECS]) of children aged 8 years. The clinical history of allergic diseases, measles, and the concentration of measles immunoglobulin G titers in serum enzyme immunoassay were examined. Fisher's exact tests were used to assess the relationships between the allergic characteristics of the children and their measles antibody positivity rates., Results: This study included 162 children. Any allergic disease was reported in 75 (46.3%). The measles antibody positivity rate was 94.7% among children with any allergic diseases and 92.0% among children without allergic diseases. Our results revealed no differences in measles antibody seropositivity between children with allergies and controls., Conclusions: Children with allergies mount and maintain a comparable immune response to the measles vaccine., Competing Interests: The authors have declared that no competing interests exist.

The increase of the evolutionary pressure will cause phylodynamics changes of viruses. In post-vaccine coverage era, measles viruses face more immune pressure than ever before. Vice versa, the phylodynamic changes may reflect herd immunity level provided by vaccination. In this study, we analyzed phylodynamic characteristics of measles viruses isolated from 2005 to 2017 in Jiangsu province of China using nucleoprotein gene sequences of measles viruses. The phylogenetic tree was constructed with Markov chain Monte Carlo algorithm. The mean gene distance within each group was computed with MEGA7.0 software. Our results showed that a decline trend is observed in the gene distance of nucleoprotein gene with time as well as incidence of measles from epidemic surveillance system. Two clusters of H1a genotype show cocirculation of multiple variants in early years and the disappearance of most variants with time. We explore the phylodynamic of measles virus under high immune pressure. Our findings highlight that phylodynamic of measles viruses is a helpful tool to assess the effectiveness of epidemic control., (© 2021 Wiley Periodicals LLC.)

It has been proven that post-vaccination immunity to measles virus after two doses of vaccine is not able to persistently protect against infection throughout life. The goal of this research was to determine the immune layer to the measles virus among women in labor and maternity ward personnel in the same medical institution. The levels of IgG antibodies to measles virus in the umbilical cord blood of 594 women in labor and 88 workers of the maternity ward were studied by ELISA. It was revealed that 22.7% of umbilical cord blood serum samples from parturient women and 21.4% of blood serum samples from maternity ward personnel were seronegative (<0.18 IU/ml). Levels of IgG antibodies to measles virus in low values (<1.0 IU/ml) were detected in 67% of blood serum samples among women in labor and 68.9% among employees of the maternity ward. Among women in labor, women under 35 years of age are at the highest risk of contracting measles; the proportion of women with low levels of protective antibodies in this age group was almost 70%, and the proportion of women without protective levels of antibodies was 23%. Compared with the age group 36-43, the age of women in labor under 35 was associated with a higher chance of not having immune protection against infection with measles virus OR [95% CI] = 2.2 [1.1-4.5] (p = 0.02) or had a low level of protection OR [95% CI] = 1.9 [1.2-3.0] (p = 0.001). It was also found that among women over 35 years of age, the proportion of persons with a high level of antibodies in women in labor was statistically significantly higher than among members of the maternity ward staff (13 and 0%, respectively, p = 0.007). Thus, maternity ward employees and women in labor constitute a risk group for measles due to the presence of a high proportion of seronegative persons among women of childbearing age (both maternity ward employees and women in labor). These conditions create the need to revise current approaches to present vaccination procedures, especially in the current epidemiological situation with COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kostinov, Zhuravlev, Gladkova, Mashilov, Polishchuk, Shmitko, Zorina, Blagovidov, Pahomov, Vlasenko, Ryzhov and Khromova.)

Since the elimination of the measles virus, patients with vaccination records for the measles-containing vaccine have increased in Japan. According to several studies, the transmission risk from previously immunized patients, especially those with secondary vaccine failure (SVF), is lower than that from those with primary measles infections. Immunological features of SVF were identified per specific immunoglobulin G (IgG) induction with high avidity and high plaque reduction neutralization antibody concentration. However, the virological features of SVF have not been well investigated. To examine not only immunological but also virological differences between SVF and immunologically naive patients, throat swabs and blood and urine specimens of 25 patients with confirmed measles infection after an outbreak at the Kansai International Airport in 2016 were analyzed. Patients were categorized as naive (n = 3) or with SVF (n = 22) based on measles-specific IgG antibody concentrations and their avidity. Virus isolation and quantitative real-time polymerase chain reaction were performed to quantify the viral load in clinical specimens and estimate the infectivity in each specimen. The number of viral genome copies in the blood specimens of those with SVF was significantly different and approximately 1 out of 100 of that in immunologically naive patients. However, genome copy numbers in throat swabs and urine specimens were not significantly different between the groups. The virus was isolated only from those in the naive group. Our study indicated low transmission risk of the virus in patients with SVF., (© 2020 Wiley Periodicals LLC.)

Background: Measles vaccinations have been suggested to provide immune protection and decreased measles incidence. However, there was a limited study evaluating how the measles vaccine elicits specific immune responses., Objective: This study aimed to evaluate both humoral and cellular immunity to first-dose measles vaccine Edmonston-Zagreb (EZ) in 9-month-old Indonesian infants., Methods: A cohort study was conducted on 9-month-old infants who got the first-dose of measles vaccine EZ. Measles-specific immunoglobulin G (IgG) antibody serum levels were measured using plaque-reduction microneutralization assay. Peripheral blood mononuclear cells were stimulated with a measles-specific peptide to identify a cellular immune response. Quantification of CD4 + and CD8 + T-cells producing interferon-gamma (IFN-ɣ) and interleukin 17-A (IL-17A) were conducted by flow cytometry. Humoral and cellular immune response parameters were analyzed over time., Results: The prevalence of seropositivity rates was 85.8% at 1-month after vaccination and 16.67% at 6-months postvaccination. Measles-specific IgG antibodies increased significantly at 1-month after measles vaccination. However, they decreased significantly 6-months after vaccination. IFN-ɣ and IL-17A secreting T-cells increased significantly at 1-month after measles vaccination. Interestingly, a significant decrease of IFN-ɣ and IL-17A secreting CD4 + T cells was noticed 6-months postvaccination compared to IFN-ɣ and IL-17A secreting CD8 + T cells., Conclusion: Our study suggests that the first-dose measles vaccine on 9-months-old infants seems to induce both humoral and cellular immune responses that decline 6-months after vaccination.

After centuries of pestilence and decades of global vaccination, measles virus (MeV) genotypes capable of evading vaccine-induced immunity have not emerged. Here, by systematically building mutations into the hemagglutinin (H) glycoprotein of an attenuated measles virus strain and assaying for serum neutralization, we show that virus evolution is severely constrained by the existence of numerous co-dominant H glycoprotein antigenic sites, some critical for binding to the pathogenicity receptors SLAMF1 and nectin-4. We further demonstrate the existence in serum of protective neutralizing antibodies targeting co-dominant fusion (F) glycoprotein epitopes. Lack of a substantial reduction in serum neutralization of mutant measles viruses that retain even one of the co-dominant antigenic sites makes evolution of pathogenic measles viruses capable of escaping serum neutralization in vaccinated individuals extremely unlikely., Competing Interests: M.Á.M.-A. and S.J.R. are inventors in a patent application filed by the Mayo Clinic relating to the virus described in this report (WO2018212842A1) that has been out-licensed. S.J.R. is a founder and equity holder of Vyriad., (© 2021 The Author(s).)

Background: Case fatality ratio (CFR) among all age groups during the 2016-2018 measles outbreak in Romania was increased compared with previous outbreaks. To identify risk factors for measles death, we conducted a case-control study among infants and children hospitalized for measles., Methods: National surveillance data were used to identify hospitalized cases of laboratory-confirmed or epidemiologically linked measles in infants and children aged < 59 months with rash onset from January 2016 to July 2018. We abstracted medical records of 50 fatal cases ("cases") and 250 non-fatal cases ("controls") matched by age, sex, district of residence, and urban/rural place of residence. We calculated univariable and multivariable matched odds ratios (OR) and 95% confidence intervals (CIs) for risk factors., Results: Ninety-three percent of case-patients and controls had not received a valid dose of a measles-containing vaccine; only 5 % received Vitamin A supplementation once diagnosed with measles. In the univariable analysis, cases were more likely than controls to have had a healthcare-related exposure to measles manifesting as inpatient admission for pneumonia during the 7 to 21 day measles incubation period (OR: 3.0; 95% CI [1.2, 7.2]), to have had a history of malnutrition (OR: 3.4; 95% CI [1.1, 9.9]), and to have had pneumonia as a complication of measles (OR:7.1; 95% CI [2.0-24.8]). In the multivariable analysis, pneumonia as a measles complication remained a risk for death (OR: 7.1; 95% CI [1.4-35.3])., Conclusions: Implementing infection prevention and control practices, ensuring immunization of healthcare workers, and hospitalizing only severe measles cases may minimize the risk of nosocomial measles transmission. Implementing World Health Organization (WHO) recommendations for Vitamin A supplementation, improving immunization of children to prevent influenza, pneumococcal, and other bacterial respiratory diseases may decrease complications and deaths due to measles in Romania.

We investigated whether countries with higher coverage of childhood live vaccines [BCG or measles-containing-vaccine (MCV)] have reduced risk of coronavirus disease 2019 (COVID-19)-related mortality, while accounting for known systems differences between countries. In this ecological study of 140 countries using publicly available national-level data, higher vaccine coverage, representing estimated proportion of people vaccinated during the last 14 years, was associated with lower COVID-19 deaths. The associations attenuated for both vaccine variables, and MCV coverage became no longer significant once adjusted for published estimates of the Healthcare access and quality index (HAQI), a validated summary score of healthcare quality indicators. The magnitude of association between BCG coverage and COVID-19 death rate varied according to HAQI, and MCV coverage had little effect on the association between BCG and COVID-19 deaths. While there are associations between live vaccine coverage and COVID-19 outcomes, the vaccine coverage variables themselves were strongly correlated with COVID-19 testing rate, HAQI and life expectancy. This suggests that the population-level associations may be further confounded by differences in structural health systems and policies. Cluster randomised studies of booster vaccines would be ideal to evaluate the efficacy of trained immunity in preventing COVID-19 infections and mortality in vaccinated populations and on community transmission.

Background: The measles Supplementary Immunization Activity (SIA) was implemented in June, 2017 to close immunity gaps by providing an additional opportunity to vaccinate children aged between 9 months and up to 14 years in Lilongwe District, Malawi. This study was conducted to determine the proportion of eligible children that were reached by the 2017 measles SIA among those children with or without history of measles vaccination, and possible reasons for non-vaccination., Methods: A cross-sectional survey using mixed methods was conducted. Caretakers of children who were eligible for the 2017 measles SIA were sampled from 19 households from each of the 25 clusters (villages) that were randomly selected in Lilongwe District. A child was taken to have been vaccinated if the caretaker was able to explain when and where the child was vaccinated. Eight Key Informant Interviews (KIIs) were conducted with planners and health care workers who were involved in the implementation of the 2017 measles SIA. Modified Poisson regression was used to examine the association between non-vaccination and child, caretaker and household related factors. A thematic analysis of transcripts from KIIs was also conducted to explore health system factors associated with non-vaccination of eligible children in this study., Results: A total of 476 children and their caretakers were surveyed. The median age of the children was 52.0 months. Overall, 41.2% [95% CI 36.8-45.7] of the children included in the study were not vaccinated during the SIA. Only 59.6% of children with previous measles doses received SIA dose; while 77% of those without previous measles vaccination were reached by the SIA. Low birth order, vaccination history under routine services, low level of education among caretakers, unemployment of the household head, younger household head, provision of insufficient information by health authorities about the SIA were significantly associated with non-vaccination among eligible children during the 2017 measles SIA. Qualitative findings revealed strong beliefs against vaccinations, wrong perceptions about the SIA (from caretakers' perspectives), poor delivery of health education, logistical and human resource challenges as possible reasons for non-vaccination., Conclusion: Many children (41%) were left unvaccinated during the SIA and several factors were found to be associated with this finding. The Lilongwe District Health Team should endeavor to optimize routine immunization program; and community mobilization should be intensified as part of SIA activities., Competing Interests: The authors have declared that no competing interests exist.

The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.

Objectives: The World Health Organization pre-qualified single-dose typhoid conjugate vaccine (TCV) and requested data on co-administration with routine vaccines. The co-administration of Typbar TCV (Bharat Biotech International) with routine group A meningococcal conjugate vaccine (MCV-A) and measles-rubella (MR) vaccine was tested., Methods: This was a double-blind, randomized controlled trial performed in Ouagadougou, Burkina Faso. Children were recruited at the 15-month vaccination visit and were assigned randomly (1:1:1) to three groups. Group 1 children received TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; group 2 children received TCV and MCV-A; group 3 children received MCV-A and control vaccine. Routine MR vaccine was administered to all participants. Safety was assessed at 0, 3, and 7 days after immunization, and unsolicited adverse events and serious adverse events were assessed for 28 days and 6 months after immunization, respectively., Results: A total of 150 children were recruited and vaccinated. Solicited symptoms were infrequent and similar for TCV and control recipients, as were adverse events (group 1, 61.2%; group 2, 64.0%; group 3, 68.6%) and serious adverse events (group 1, 2.0%; group 2, 8.0%; group 3, 5.9%). TCV generated robust immunity without interference with MCV-A vaccine., Conclusions: TCV can be safely co-administered at 15 months with MCV-A without interference. This novel study on the co-administration of TCV with MCV-A provides data to support large-scale uptake in sub-Saharan Africa., (Published by Elsevier Ltd.)

The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8 + and CD4 + T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Breast cancer is the most commonly diagnosed cancer and is the second leading cause of death in women. However, resistance to radio‑ and chemotherapy remains one of the major difficulties in the treatment of breast cancer. Therefore, the aim of the present study was to identify novel regimens to overcome treatment resistance in patients with breast cancer. The results of the present study demonstrated that the attenuated Edmonston‑B vaccine strain of the measles virus (MV‑Edm) significantly re‑sensitized breast cancer cells to doxorubicin and ionizing radiation. Mechanistically, MV‑Edm reduced DNA double strand repair efficiency by decreasing the mRNA and protein expression levels of p53‑binding protein 1 and disassembling the non‑homologous end joining (NHEJ) complex. NHEJ deficiency, which was achieved using DNA ligase IV knockout via CRISPR/Cas9, resulted in failure to overcome resistance mediated by MV‑Edm infection. As a result of the significant synergy between attenuated MV and radio‑ or chemotherapy, MV‑Edm provides a novel strategy for the treatment of radio‑ and chemoresistant breast cancer.

Background: Border areas are at high risk of measles epidemics. This study aimed to evaluate the effectiveness of the implementation of the routine two-dose measles containing vaccine (MCV) program in border counties of Southwest China., Methods: Data used in the study were derived from a cross-sectional survey among 1,467 children aged 8 to 84 months from five border counties of Yunnan Province, Southwest China in 2016. The participants were recruited using a multistage sampling method. Primary guardians of the children were interviewed to collect information on vaccination history, socio-economic status, and knowledge about immunization. Both coverage and timely coverage for the first (MCV1) and the second (MCV2) dose of MCV were calculated. The Kaplan-Meier method was performed to estimate the cumulative coverage of MCV, and Log-rank tests were adopted to compare the differences across counties and birth cohorts. Univariate and multivariate logistic regression models were used to investigate the predictors of delayed MCV1 vaccination., Results: The coverage for MCV1 and MCV2 were 97.5% and 93.4%, respectively. However, only 63.8% and 84.0% of the children received MCV1 or MCV2 on time. Significant differences in the cumulative coverage were detected across counties and birth cohorts. Results of the multivariate logistic regression analysis indicated that children whose primary guardian knew the schedule of MCV were less likely to receive MCV1 late (OR = 0.63, P<0.01). For the guardians, doctors at vaccination units were the primary and also the most desired source of vaccination information., Conclusions: Although the coverage for MCV is high in border areas of Southwest China, the timeliness of MCV vaccination seems suboptimal. Tailored information from local health professionals may help to reduce untimely vaccination., Competing Interests: The authors have declared that no competing interests exist.

Measles vaccination is a public health 'best buy', with the highest cost of illness averted of any vaccine-preventable disease (Ozawa et al., Bull. WHO 2017;95:629). In recent decades, substantial reductions have been made in the number of measles cases, with an estimated 20 million deaths averted from 2000 to 2017 (Dabbagh et al., MMWR 2018;67:1323). Yet, an important feature of epidemic dynamics is that large outbreaks can occur following years of apparently successful control (Mclean et al., Epidemiol. Infect. 1988;100:419-442). Such 'post-honeymoon period' outbreaks are a result of the nonlinear dynamics of epidemics (Mclean et al., Epidemiol. Infect. 1988;100:419-442). Anticipating post-honeymoon outbreaks could lead to substantial gains in public health, helping to guide the timing, age-range, and location of catch-up vaccination campaigns (Grais et al., J. Roy. Soc. Interface 2008003B6:67-74). Theoretical conditions for such outbreaks are well understood for measles, yet the information required to make these calculations policy-relevant is largely lacking. We propose that a major extension of serological studies to directly characterize measles susceptibility is a high priority., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Ethiopia has low measles immunization coverage and little is known about the disparities surrounding what coverage is provided. This study assessed disparities in measles immunization and its change over time using the four Ethiopia Demographic and Health Surveys conducted between 2000 and 2016., Methods: This is a cross-sectional analysis of data using Ethiopia Demographic and Health Surveys (EDHS) conducted between 2000 and 2016. We used the World Health Organization's (WHO) Health Equity Assessment Toolkit (HEAT) to present the inequalities. Four measures of inequality were calculated: Difference (D), Ratio (R), Population Attributable Fraction (PAF) and Population Attributable Risk (PAR). The results were disaggregated by wealth, education, residence, sex and sub-national regions and 95% Uncertainty Intervals (UIs) were computed for each point estimate to boost confidence of the findings., Results: Measles immunization coverage was higher among the richest and secondary and above schools' subgroup by nearly 30 to 31 percentage points based on point estimates (D = 31%; 95% CI; 19.48, 42.66) and 29.8 percentage points (D = 29.8%; 95% CI; 16.57, 43.06) as compared to the poorest and no education subgroup respectively in the 2016 survey. Still, in the 2016 survey, substantial economic status (PAF = 36.73; 95%CI: 29.78, 43.68), (R = 1.71; 95%CI: 1.35, 2.08), education status (PAF = 45.07; 95% CI: 41.95, 48.18), (R = 1.60; 95% CI: 1.30, 1.90), place of residence (PAF = 39.84, 95% CI: 38.40, 41.27), (R = 1.47, 95% CI: 1.20, 1. 74) and regional (PAF = 71.35, 95% CI: 31.76, 110.95), (R = 3.09, 95%CI: 2.01, 4.17) inequality were observed with both simple and complex measures. There was no statistically significant difference in the prevalence of measles immunization between male and female children in all the studied years, as indicated, for instance, by measures of PAF in 2000 (PAF = 0; 95%CI: - 6.79, 6.79), 2005 (PAF = 0; 95%CI: - 6.04, 6.04), 2011(PAF = 0; 95%CI: - 3.79, 3.79) and 2016 (PAF = 2.66; - 1.67; 6.99). Overall, the inequality of measles immunization narrowed significantly by at least some of the measures between the first and the last survey periods across all the studied subgroups., Conclusions: National, regional and district levels of government should make a pledge to reduce inequalities in coverage of measles immunization. Equity-sensitive strategies, sufficient human and financial resources as well as continued research and monitoring of immunization coverage inequalities are necessary to achieve related sustainable development goals.

Introduction: The national and international guidelines recommend evaluating all healthcare workers (HCWs) for their measles immune status and possibly vaccinating those who are seronegative., Areas Covered: We conducted a systematic review and meta-analysis in order to estimate the rate of measles susceptibility among HCWs in Italy and to explore possible options for the management of those found to be susceptible. Twenty-three studies were included in the meta-analysis. The prevalence of HCWs susceptible to measles was 11.5% (95%CI = 8.1-15.4%) and was higher in studies in which prevalence was evaluated by survey (16.7%; 95%CI = 8.9-26.3) than by the direct evaluation of blood specimens (9.1%; 95%CI = 6.2-12.5%). Occupational medicine examinations for measles screening with possible subsequent vaccination of seronegatives and the exclusion of susceptible HCWs from high-risk settings were common management strategies., Expert Opinion: HCWs susceptible to measles are an important epidemiological concern in Italy, and efforts to identify and actively offer the vaccine to this population should be increased.

Human cytomegalovirus (HCMV) infection has a profound effect on the human immune system, causing massive clonal expansion of CD8, and to a lesser extend CD4 T cells. The few human trials that have explored the effect of HCMV infection on responses to vaccination are conflicting, with some studies suggesting no effect whilst others suggest decreased or increased immune responses. Recent studies indicate substantial differences in overall immune system reactivity to vaccines based on age and sex, particularly cellular immunity. 225 nine-month old Gambian infants were immunized with diphtheria-tetanus-whole cell pertussis and/or measles vaccines. HCMV infection status was determined by the presence of CMV DNA by PCR of urine samples prior to vaccination. The effect of HCMV infection on either protective antibody immunity or vaccine-specific and overall cellular immune responses 4 weeks post-vaccination was determined, further stratified by sex. Tetanus toxoid-specific antibody responses were significantly lower in HCMV+ infants compared to their HCMV- counterparts, while pertussis, diphtheria and measles antibody responses were generally comparable between the groups. Responses to general T cell stimulation with anti-CD3/anti-CD28 as well as antigen-specific cytokine responses to purified protein derivative (PPD) were broadly suppressed in infants infected with HCMV but, perhaps surprisingly, there was only a minimal impact on antigen-specific cellular responses to vaccine antigens. There was evidence for subtle sex differences in the effects of HCMV infection, in keeping with the emerging evidence suggesting sex differences in homeostatic immunity and in responses to vaccines. This study reassuringly suggests that the high rates of HCMV infection in low income settings have little clinically significant impact on antibody and cellular responses to early life vaccines, while confirming the importance of sex stratification in such studies., (Copyright © 2020 Cox, Adetifa, Noho-Konteh, Njie-Jobe, Sanyang, Drammeh, Plebanski, Whittle, Rowland-Jones, Robertson and Flanagan.)

Background: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection., Methods: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria., Results: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold., Conclusions: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold., (© Her Majesty the Queen in Right of Canada, as represented by the Minister of Public Health Ontario, 2019.)

Background: The objectives of this review were to evaluate the effect of age at administration of the first dose of a measles-containing vaccine (MCV1) on protection against measles and on antibody response after one- and two-dose measles vaccinations., Methods: We conducted a systematic review of the PubMed/MEDLINE, Embase, Web of Science and Cochrane databases (1964-2017) to identify observational studies estimating vaccine effectiveness and/or measles attack rates by age at first vaccination as well as experimental studies comparing seroconversion by age at first vaccination. Random effect models were used to pool measles risk ratios (RR), measles odds ratios (OR) and seroconversion RR of MCV1 administered at < 9, 9-11 or ≥ 15 months compared with 12 or 12-14 months of age., Results: We included 41 and 67 studies in the measles protection and immunogenicity analyses. Older age at MCV1, from 6 to ≥15 months, improved antibody response and measles protection among one-dose recipients. Pooled measles RR ranged from 3.56 (95%CI: 1.28, 9.88) for MCV1 at < 9 months to 0.48 (95%CI: 0.36, 0.63) for MCV1 at ≥15 months, both compared to 12-14 months. Pooled seroconversion RR ranged from 0.93 (95%CI: 0.90, 0.96) for MCV1 at 9-11 months to 1.03 (95%CI: 1.00, 1.06) for MCV1 at ≥15 months, both compared to 12 months. After a second dose, serological studies reported high seropositivity regardless of age at administration of MCV1 while epidemiological data based on few studies suggested lower protection with earlier age at MCV1., Conclusions: Earlier age at MCV1 decreases measles protection and immunogenicity after one dose and might still have an impact on vaccine failures after two doses of measles vaccine. While two-dose vaccination coverage is most critical to interrupt measles transmission, older age at first vaccination may be necessary to keep the high level of population immunity needed to maintain it.