Measles Vaccine Research Articles

Measles outbreak investigation in Berhet District, North Shewa, Ethiopia.

Measles, though usually self-limiting, can have severe consequences influenced by factors such as vaccination and nutrition, notably vitamin A deficiency and malnutrition. Despite progress, contextual changes and implementation issues have hampered efforts, resulting in increased outbreaks and cases of measles. This study seeks to pinpoint outbreak features, risk factors, and strategies for preventing and controlling measles. A descriptive cross-sectional study and a 1:2 unmatched case-control study design were employed. All 101 suspected measles cases listed on the line-list were included in the descriptive research, with 60 measles patients and 120 controls included in the case-control investigation. Line-list data were cleaned and analyzed using a pivot table in Microsoft Excel 2016. Subsequently, the data were cleaned, entered into Epi Info 7.2, and exported to SPSS 26 for analysis. Twenty cases occurred per 10,000 individuals. Men accounted for 67.3% of cases, with ages ranging from 5 months to 45 years and mean and standard deviations of 9.6 and 7.6, respectively. Age group of 5-14 years comprised 57.4% of cases, followed by 1-4 years with 24.8%. Being unvaccinated against measles showed an adjusted odds ratio (AOR) of 12.06 (95% CI: 3.12-46.52). Travel history to regions with active cases had an AOR of 5.73 (95% CI: 1.78-18.38). Contact with a measles patient showed an AOR of 10.3 (95% CI: 3.48-30.5). Understanding the measles transmission mechanism had an AOR of 0.164 (95% CI: 0.049-0.55), and awareness of the disease's preventability had an AOR of 0.233 (95% CI: 0.67-0.811). All factors were independently associated with the illness. This outbreak affected a broader age range with a high attack rate, mainly in the age group of 5-14-years. Over 35% of cases lacked measles vaccination, indicating low administrative vaccine coverage. Factors contributing to the outbreak include lack of measles vaccination, travel to areas with active disease, contact with cases, and insufficient knowledge of measles transmission and prevention strategies among mothers and caregivers.

Determinants of second-dose measles vaccination dropout in Ethiopia: A community-based matched case-control study

BackgroundMeasles vaccination is the most important public health intervention and a cost-effective strategy to reduce morbidity and mortality in under-five children. Although Ethiopia's government developed a measles elimination strategic plan by 2020, the full coverage of immunization was 43 %. Therefore, this study aimed to identify determinants of second-dose measles vaccination (MCV2) dropout among children aged 24–35 months in East Bale Zone, Ethiopia. MethodA community-based matched case-control study was conducted among 351 children (117 cases and 234 controls). Children who received the first dose of measles vaccine but did not receive the second dose were cases, and children who received both doses of measles vaccine were control. The matches were based on age and residence. The data were collected using a structured questionnaire, entered into Epi Data 3.1, cleaned, exported, and analyzed using Stata version 16.1. A multivariable conditional logistic regression analysis was performed. Variables with a P value of <0.05 were considered significant determinants of the dependent variable at the 95 % confidence level. ResultsMothers who were unable to read and write (mAOR: 4.0; 95 % CI: 1.59–10.2), did not receive counseling (mAOR: 3.19; 95 % CI: 1.62–6.27), spent ≥30 min to reach health facilities (mAOR; 2.76, 95 % CI: 1.25–6.1), and did not attend postnatal care (mAOR; 3.46, 95 % CI: 1.58–7.57) were significantly and positively associated with second-dose measles vaccination dropout. In addition, mothers who had poor knowledge of second-dose measles vaccination (mAOR; 3.20, 95 % CI: 1.50–6.70) and waited more than an hour for measles vaccination at health facilities (mAOR; 2.61, 95 % CI: 1.0–6.20) were significantly more likely to experience second-dose measles vaccine dropout. ConclusionsThe key factors associated with second-dose measles vaccination dropout are maternal illiteracy, lack of PNC, inadequate maternal knowledge and poor counseling about MCV2 vaccination, long distances travel to healthcare facilities and extended waiting times at vaccination providing sites. Health extension workers emphasize strengthening home visit programs in catchment households to improve mothers' awareness of measles vaccination.

Shedding of measles vaccine RNA in children after receiving measles, mumps and rubella vaccination

BackgroundMeasles, mumps, and rubella(MMR) vaccination is critical to measles outbreak responses. However, vaccine reactions and detection of measles vaccine RNA in recently immunized persons may complicate case classification especially in those presenting with another respiratory viral illness. We aim to characterize cases of measles vaccine shedding in recently vaccinated children presenting with respiratory viral symptoms. MethodsChildren who were tested with a multiplex respiratory panel <30 days after receiving MMR were identified. Remnant nasopharyngeal(NP) samples were tested for measles vaccine by PCR. Medical records were reviewed for demographics, presenting symptoms, and test results. ResultsFrom January 2022 to March 2023, 127 NP from children who received MMR were tested. Ninety-six NP were collected after the first dose, of which 33(34.4 %) were positive for vaccine RNA. The median interval between MMR and detection was 11.0 days. Thirty-one NP were collected after the second MMR and 1(3.2 %) was positive; time between the vaccination and detection was 18.9 days. Median cycle threshold(Ct) value of the measles PCR for vaccine shedding was significantly higher than median Ct in children with wild-type infection. ConclusionShedding of measles vaccine RNA is not uncommon and vaccine RNA can be detected up to 29 days post MMR; the amount of vaccine RNA shedding is low indicated by high Ct values. Clinicians and public health officials should consider performing measles vaccine testing on those testing positive for measles within one month of MMR vaccination, especially if the Ct value is high and definitive epidemiological links are absent.

Analysis of Suspected Measles Cases with Discrepant Measles-Specific IgM and rRT-PCR Test Results, Japan.

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.

Raising Epidemiological Awareness: Assessment of Measles/MMR Susceptibility in Highly Vaccinated Clusters within the Hungarian and Croatian Population-A Sero-Surveillance Analysis.

Perceptions of the complete eradication of vaccine-preventable diseases such as measles, mumps, and rubella (MMR) may foster complacency and compromise vaccination efforts. Decreased measles vaccination rates during the COVID-19 pandemic have heightened the risk of outbreaks, even in adequately vaccinated populations. To address this, we have aligned with ECDC recommendations, leveraging previous cross-border sero-epidemiological assessments between Pécs, Hungary, and Osijek, Croatia, to identify latent risk groups and uncover potential parallels between our nations. Testing 2680 Hungarian and 1764 Croatian serum samples for anti-MMR IgG via ELISAs revealed anti-measles seropositivity ratios below expectations in Croatian cohorts aged ~20-30 (75.7%), ~30-40 (77.5%) and ~40-50 years (73.3%). Similarly, Hungarian samples also showed suboptimal seropositivity ratios in the ~30-40 (80.9%) and ~40-50 (87.3%) age groups. Considering mumps- and rubella-associated seropositivity trends, in both examined populations, individuals aged ~30-50 years exhibited the highest vulnerability. Additionally, we noted congruent seropositivity trends across both countries, despite distinct immunization and epidemiological contexts. Therefore, we propose expanding research to encompass the intricate dynamics of vaccination, including waning long-term immunity. This understanding could facilitate targeted interventions and bolster public awareness. Our findings underscore persistent challenges in attaining robust immunity against measles despite vaccination endeavors.

Case Ascertainment of Measles during a Large Outbreak-Laboratory Compared to Epidemiological Confirmation.

Measles is a highly contagious viral disease, and hence, sufficient herd immunity is obligatory to prevent infection transmission. Measles is still a cause of considerable disease burden globally, mainly in children. During a national measles outbreak in Israel in 2018-2019, the peak incidence rates occurred in the Jerusalem district. Most measles cases in the Jerusalem district (75.5%, 1702) were observed in children younger than 15 years of age, 49.2% (1109) were in children under 5 years of age, and 18.9% (425) were in infants under 1 year of age. The routine measles vaccination schedule includes two doses at 1 and 6 years of age. Most cases (1828, 81.1%) were unvaccinated (zero measles vaccine doses). These cases comprised the 425 affected infants under 1 year of age, who were ineligible for vaccination, along with the 1403 children over 1 year of age, who were otherwise unvaccinated. This study aimed to describe the epidemiologic and laboratory features of this measles outbreak, and to investigate case ascertainment (laboratory confirmed compared to epidemiologically confirmed cases). The study population included 2254 measles cases notified during the period spanning June 2018 to May 2019 in the Jerusalem district (incidence rate 176 per 10,000 population). Of the 2254 cases, 716 (31.8%) were laboratory confirmed, and 1538 (68.2%) were confirmed as epidemiologically linked. Most laboratory confirmed cases (420, 58.7%) underwent real-time PCR tests. Serological tests (measles IgM and IgG) were used in 189 (26.4%) cases, and a combination of RT-PCR and serology was used in 107 (14.9%) cases. In a multivariate model analysis, the variables significantly associated (after adjustment) with higher odds for laboratory confirmation included month of disease onset (late), additional measles cases in the household (single case), place of medical treatment (hospital; either emergency department, or hospitalization) and vaccination status (at least one prior vaccine dose). The measles outbreak described demonstrates the urgency of addressing vaccination gaps with appropriate outbreak prevention programs. The road to measles elimination needs to be paved with robust public health infrastructure, excellent field epidemiology for outbreak surveillance, investigation, and control, and laboratory proficiency.

Epidemiological study of the occurrence of measles in children aged 0-15 years in the Banalia Health Zone (DR Congo) during 2022

Introduction: In 2021, the Banalia Health Zone experienced two measles epidemics with a vaccine completeness rate of 69% according to data provided by the Tshopo Provincial Health Division. The aim of the study was to list the epidemiological characteristics of measles cases in the Banalia Health Zone, to determine the incidence of measles in children aged 0-15 years, and to analyze the vaccination status of children with measles. Methodology: This was a retrospective descriptive study, based on the acquisition of data from the medical records of the targeted children or from data registers at the time of submission. A total of 3,968 children with measles were selected from the various health centers and areas of the Banalia Health Zone. Results: We observed that 64.6% of the subjects in the study were aged between 0 and 5 years; 40.77% of measles cases were recorded in September 2022. The measles vaccination rate was 39.19% and the case fatality rate was 2.8%. The Panga 2 axis had the highest number of measles cases, with a prevalence rate of 29.03%. Conclusion: Measles is a major cause of morbidity and mortality in the Banalia Health Zone. The age group most affected is 0-5 years. Vaccination and surveillance systems need to be strengthened to reduce the growing risk posed by measles.

A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial

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. 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. 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. The safety and immunogenicity data support the accelerated development of the MRV-MNP. Bill & Melinda Gates Foundation.

Assessing the Impact of the COVID-19 Pandemic on Pregnant Women's Attitudes towards Childhood Vaccinations: A Cross-Sectional Study.

The COVID-19 pandemic has globally disrupted immunisation practices, impacting vulnerable populations such as pregnant women (PW), who harbour concerns about future children's immunisations. This study aimed to assess the pandemic's impact on PW's attitudes towards childhood vaccinations. During three consecutive flu seasons from October 2019 to January 2022, a cross-sectional study was conducted in a large Italian teaching hospital using a questionnaire. The chi-square test was performed to compare each season. Across the 2019-2020 to 2021-2022 seasons, course attendance by PW surged from 105 to 340. Significant shifts in vaccination intentions were noted, including a 7.5% decrease in measles vaccination intent (p = 0.02) and a 10% decrease in that of pertussis (p = 0.004) from 2019-2020 to 2020-2021. While perceived contagion risk decreased, disease severity perceptions increased, with few significant differences. A statistically significant reduction was noted in the proportion of participants suspecting economic motives behind NHS workers' promotion of childhood vaccinations. Furthermore, the pandemic period saw an increase in the perceived utility of non-institutional websites and the advice of physicians outside the NHS. These findings will help develop evidence-based, tailored interventions and communication strategies to address vaccine hesitancy and ensure optimal vaccination coverage among children born during and after the pandemic.

Information on Measles, Mumps and Rubella Vaccine in the Copenhagen School Health Records Register.

The Copenhagen School Health Record Register (CSHRR) includes health information from school examinations and is now updated with information on measles, mumps and rubella vaccines for the cohorts born from 1977 to 1994. The aim of this study is to provide a comprehensive description and validation the newly digitised vaccine information in the CSHRR. We describe the data collection and the newly digitalised information in the CSHRR. We investigate the extent to which the full CSHRR population is representative of Copenhagen and the entire Danish population. Furthermore, we explore how the registry information on vaccination uptake based on reimbursement data matches the vaccine information obtained from CSHRR for the period during which both data are available. The CSHRR population matches closely the complete population of all schoolchildren in Copenhagen, and information on vaccine uptake in CSHRR matches with vaccine registry data for later cohorts. However, a sizable proportion of the immigrant children in the CSHRR have missing information on vaccination. Removing children who have had no additional immunisations enhances data quality. The CSHRR covers a large share of the Danish population and includes detailed vaccine information. By linking the data to other registry data, the updated CSHRR is valuable resource for future research.

Изучение распространенности и клинических проявлений коревой инфекции на современном этапе

Today, the issue of measles is of great importance, since cases of this disease are currently increasingly common. Insufficient immunization coverage and the increase in the rate of measles vaccine refusal are considered to be the main cause of the incidence increase. Furthermore, it is important to note that an almost high rate of the atypical course of measles, specifically the emergence of the trend towards fusion of the rash, itching, no pigmentation period, no pathognomonic symptom (Belsky–Filatov–Koplik spots), the emergence of hepatomegaly, increased liver transaminases, and the development of diarrhea, is reported at the current stage. It is impossible to ignore the fact that measles can lead to severe complications, such as pneumonia, encephalitis, meningitis, hepatitis, etc. Measles can also be fatal, thereforore, it is necessary to understand the importance of prevention, timely treatment and diagnosis of this disease.

COVID-19 epidemiology, health services utilisation and health care seeking behaviour during the first year of the COVID-19 pandemic in Mweso health zone, Democratic Republic of Congo.

Although the evidence about coronavirus disease 2019 (COVID-19) has increased exponentially since the beginning of the pandemic, less is known about the direct and indirect effects of the pandemic in humanitarian settings. In the Democratic Republic of the Congo (DRC), most studies occurred in Kinshasa and other cities. Limited research was conducted in remote conflict-affected settings. We investigated the COVID-19 epidemiology, health service utilisation, and health care-seeking behaviour during the first year of the pandemic (March 2020-March 2021) in the Mweso health zone, North Kivu, DRC. This mixed-methods study includes a descriptive epidemiological analysis of reported COVID-19 cases data extracted from the provincial line list, interrupted time series analysis of health service utilisation using routine health service data, qualitative perceptions of health care workers about how health services were affected, and community members' health care seeking behaviour from a representative household survey and focus group discussions. The COVID-19 epidemiology in North Kivu aligns with evidence reported globally, yet case fatality rates were high due to underreporting. Testing capacity was limited and initially mainly available in the province's capital. Health service utilisation showed different patterns - child measles vaccinations experienced a decrease at the beginning of the pandemic, while outpatient consultations, malaria, and pneumonia showed an increase over time. Such increases might have been driven by insecurity and population displacements rather than COVID-19. Community members continued seeking care during the first months of the COVID-19 pandemic and visited the same health facilities as before COVID-19. Financial constraints, not COVID-19, were the main barrier reported to accessing health care. The first year of the COVID-19 pandemic in the Mweso health zone was characterised by low testing capacity and an underestimation of reported COVID-19 infections. The increase in health care utilisation should be further explored to understand the role of factors unrelated to COVID-19, such as insecurity, population displacement, and poverty, which remain major challenges to successfully providing health services and improving the population's health. Measles vaccination coverage dropped, which exacerbated the ongoing measles outbreak. Improved decentralised testing capacity will be crucial for future epidemics and enhanced efforts to maintain child vaccination coverage.

Measles, mumps, and rubella vaccination coverage: an ecological study of primary health care and socio-economic factors in Catalonia, Spain.

This study examined the association of socio-economic factors and the structure of primary care centres (PCCs) with measles, mumps, and rubella (MMR) vaccination coverage among the 8-year-old population in Catalonia, Spain. We conducted an ecological study to retrospectively assess the MMR vaccination-recorded status of children born in 2012, using public health data extracted in December 2020. For each of 300 PCCs serving 70,498 children, we calculated vaccination coverage rates from electronic health records and linked these rates to a composite deprivation index corresponding to the territory served by each PCC. We identified a relationship between unfavourable socio-economic factors and higher recorded vaccination coverage. On average, directly managed PCCs had higher vaccination coverage rates than indirectly managed PCCs. Greater utilisation of primary care services by the population was also associated with higher vaccination coverage rates. Further research is needed to generate knowledge valuable for informing more equitable child-vaccination service delivery models.

Measles Vaccine Coverage and Disease Outbreaks: A Systematic Review of the Early Impact of COVID-19 in Low and Lower-Middle Income Countries.

Objectives: We aimed to evaluate changes to measles-containing vaccine (MCV) provision and subsequent measles disease cases in low- and lower-middle income countries (LICs, LMICs) in relation to the COVID-19 pandemic. Methods: A systematic search was conducted of MEDLINE, OVID EMBASE and PubMed records. Primary quantitative and qualitative research studies published from January 2020 were included if they reported on COVID-19 impact on MCV provision and/or measles outbreak rates within LICs and LMICs. Results: 45 studies were included. The change in MCV1 vaccination coverage in national and international regions ranged -13% to +44.4% from pre-COVID time periods. In local regions, the median MCV1 and overall EPI rate changed by -23.3% and -28.5% respectively. Median MCV2 rate was disproportionally impacted in local areas during COVID-interruption time-periods (-48.2%) with ongoing disruption in early-recovery time-periods (-17.7%). 8.9% of studies reported on vaccination status of confirmed measles cases; from these, 71%-91% had received no MCV dose. Conclusion: MCV vaccination coverage experienced ongoing disruption during the recovery periods after initial COVID-19 disruption. Vaccination in local area datasets notably experienced longer-term disruption compared to nationally reported figures.

Detection of measles vaccine virus and measles-specific immunoglobulin M in children vaccinated against measles-mumps-rubella during measles outbreak

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

Comprehensive Outreach: Reach Every Child Initiative Expanded Program on Immunization Khyber Pakhtunkhwa, Pakistan

Background: Vaccination is one of the most effective public health interventions for preventing infectious diseases. In regions like Khyber Pakhtunkhwa, Pakistan, where access to healthcare is limited, immunization coverage often remains below optimal levels. Targeted outreach activities can play a pivotal role in improving vaccine uptake, particularly in underserved populations. Objective: This study aimed to assess the effectiveness of immunization outreach activities in increasing vaccine coverage in Khyber Pakhtunkhwa over a defined period. Methods: A comprehensive methodological approach was utilized involving predefined Excel sheets for daily data collection by trained personnel. Data validation procedures were implemented to ensure accuracy, with regular feedback sessions to improve data collection processes. Monthly reports were compiled and analyzed using SPSS version 25 to summarize immunization activities and coverage rates. The outreach strategy included community announcements and door-to-door campaigns by Local Health Workers (LHWs), designed to identify and vaccinate zero-dose and defaulting children. Results: The outreach campaign significantly improved immunization coverage, with zero-dose vaccinations achieving 100% coverage. Penta I, II, and III vaccines saw coverage rates of 78.99%, 72.48%, and 78.02%, respectively. Measles vaccines MCV-I and MCV-II achieved coverage rates of 83.01% and 86.11%. The overall strategy effectively reduced gaps in vaccine coverage across various districts. Conclusion: The study confirms that structured and well-coordinated outreach activities can effectively increase immunization coverage in areas with limited healthcare access. Continuous effort and strategic planning are essential to sustain and build upon these gains to ensure comprehensive vaccine coverage.

Meta-Analysis the Effect of Protected Well and Measles Vaccination on Stunting in Children Under Five

Meta-Analysis the Effect of Protected Well and Measles Vaccination on Stunting in Children Under Five

Correlations between History of Contact with Infected Person and Measles Vaccination Status on the Risk of Measles Incidence in Children: Meta-Analysis

Correlations between History of Contact with Infected Person and Measles Vaccination Status on the Risk of Measles Incidence in Children: Meta-Analysis

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: candidate selection in a preclinical murine model.

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.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.