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.

Acute Pancreatitis Induced by COVID-19 Vaccine: A Systematic Review.

Acute pancreatitis, marked by sudden inflammation of the pancreas, presents a complex spectrum of causative factors including gallstone obstruction, alcohol abuse, and viral infections. Recent studies have illuminated the emergence of vaccine-induced acute pancreatitis, notably associated with COVID-19 vaccinations, presenting diverse mechanisms ranging from direct viral-mediated injury to autoimmune reactions. Understanding this link is pivotal for public health, yet challenges persist in identifying and managing cases post-vaccination. Comprehensive literature reviews employing the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement outline the potential pathways and mechanisms leading to vaccine-induced pancreatitis, emphasizing the need for deeper investigations into underlying health conditions and modifications to vaccine components. Notably, the rare occurrences of vaccine-induced pancreatitis extend beyond COVID-19 vaccines, with reports also documenting associations with measles, mumps, and rubella (MMR), human papillomavirus (HPV), and other viral vaccinations. Mechanistically, hypotheses such as molecular mimicry and immunologic injury have been proposed, necessitating ongoing vigilance and exploration. Regulatory agencies play a crucial role in monitoring and communicating vaccine safety concerns, emphasizing transparency to address potential risks and maintain public trust. Understanding and communicating these rare adverse events with transparency remain integral for informed vaccination policies and to allay concerns surrounding vaccine safety.

Increased reports of measles in the Metropolitan City of Milan, northern Italy, September 2023 to March 2024.

Since late 2023, the Metropolitan City of Milan and surrounding areas (northern Italy) have been experiencing a resurgence of measles, with most cases detected starting from January 2024. During this brief period, we observed measles in travellers from endemic areas, participants in international events, vaccinees and healthcare workers. Indigenous cases have also been identified. Even though we have not yet identified large and disruptive outbreaks, strengthening surveillance and vaccination activities is pivotal to help limit the impact of measles spread.

Rapid molecular epidemiology investigations into two recent measles outbreaks in Israel detected from October 2023 to January 2024.

Between late 2023 and early 2024, two measles outbreaks occurred in Israel, each caused by importation of measles virus strains of respective B3 and D8 genotypes. In this study, we validate transmission pathways uncovered by epidemiological investigations using a rapid molecular approach, based on complete measles virus genomes. The presented findings support this rapid molecular approach in complementing conventional contact tracing and highlight its potential for informing public health interventions.

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.

Assessment of Knowledge of Communicable Diseases Among Medical Students at Al-Balqa Applied University.

INTRODUCTION: Medical education is the foundation of knowledge among medical students. This study aims to investigate the knowledge of medical students at Al-Balqa Applied University, exploring their awareness of five communicable diseases, namely, leishmaniasis, hepatitis B, tuberculosis, measles, and cholera. METHODS: This cross-sectional survey included 271 participants who answered a structured validated questionnaire with varying questions on causes, symptoms, complications, transmission routes, and preventive measures for each disease. RESULTS: Knowledge of all five communicable diseases was low. Leishmaniasis knowledge was notably low (mean=6.07, SD=1.43), with participants grappling with misconceptions about transmission modes, symptoms, and preventability. Hepatitis B knowledge was also low (mean=10.46, SD=1.67), especially regarding transmission modes, revealing that 76% of students were unaware of how the virus spreads. Tuberculosis knowledge unveiled gaps (mean=7.007, SD=1.90), particularly in recognizing the causes, symptoms, and transmission routes. Measles knowledge (mean=9.56, SD=1.92) indicated a robust understanding of symptoms but unveiled misconceptions about complications and transmission routes. For cholera (mean=14.50, SD=1.98), a knowledge of symptoms was demonstrated, but confusion about causative agents, transmission routes, and preventive measures was highlighted. CONCLUSION: The findings of the study emphasize the critical need for enhanced educational strategies including curriculum revisions, increased practical exposure, engaging awareness campaigns, and the integration of interactive learning methods to increase knowledge about communicable diseases.

Measles outbreak in the adult age group: Clinical, laboratory, and epidemiological features of the 11 patients admitted to the hospital.

The measles virus, also known as the morbillivirus, or MV, is a virus that infects humans. The goal of this research is to assess to adult cases of measles. Eleven patients thought to be confirmed cases of measles were enrolled in the investigation. Following the identification of symptoms of tiredness, fever, and rash in one soldier, the results of 10 more troops from the pertinent military group were assessed. The diagnosis was made based on the presence of serum immunoglobulin M (IgM) and positive polymerase chain reaction (PCR) results. When the control IgM, immunoglobulin G, and PCR findings were evaluated a fortnight after hospitalization, a cluster of 11 incidents was found. It is now necessary to address the issue of the cautious stance towards vaccination or the anti-vaccination sentiment that has grown increasingly popular, particularly in light of the COVID-19 pandemic, for both our nation and the entire world.

An Upsurge of Measles Cases in Mali-a Consequence of Pandemic-associated Disruption in Routine Immunization.

Measles deaths highlight immunization program gaps. In the Child Health and Mortality Prevention Surveillance study in Mali, we observed a rise in under-5 measles-related deaths in 2022 that corresponded with increased measles cases at the same time and a decline in measles vaccine coverage in Mali in 2020.

A real-world study on the changing characteristics of measles antibodies in premature infants in China.

The waning of maternal antibodies may cause infants to lose protection against measles before receiving measles-containing vaccine (MCV). The aim of this study is to investigate the changing characteristics and influencing factors of measles antibodies in preterm infants (PT), and to provide scientific basis for optimizing MCV vaccination strategy of the target population. Blood samples were collected from PT and full-term infants (FT) at the chronological age (CA) of 3, 6, and 12 months. Measles antibodies were quantitatively detected by enzyme-linked immunosorbent assay. Demographic and vaccination information were both collected. Kruskal-Wallis rank sum test was used to compare the measles antibodies among different gestation age (GA) groups, and multiple linear regression was performed to identify the correlative factors for the antibodies. Measles antibodies of PT decreased significantly with age increasing before MCV vaccination. The positive rates of antibodies of PT were 10.80% and 3.30% at the age of 3 and 6 months, respectively (p < .001). At 12 months, the measles antibodies and seropositive rate in the infants who received MCV vaccination increased sharply (p < .001). Regression analyzes showed that the younger the GA or the older the age, the lower the antibodies at 3 months(p < .001，p = .018); while the lower measles antibody levels at 3 months and older age predicted the lower antibodies at 6 months(p < .001, p = .029). PT were susceptible to measles due to the low level of maternally derived antibodies before MCV vaccination. More efforts should be considered to protect the vulnerable population during their early postnatal life.

Adverse events following Measles-Mumps-Rubella and varicella immunization: A safety profile analysis and comparison of different vaccination schedules based on the Italian Pharmacovigilance Network in the Veneto Region.

Objective: The vaccines for measles, mumps, rubella and varicella (MMR and V) have been mandatory in Italy since 2017. Two different vaccination strategies are suggested for the first dose: trivalent MMR and a separate V vaccine or the tetravalent MMRV vaccine. Our aim is to compare the safety profile of MMRV and MMR-V vaccines through the passive adverse event reporting system in the Veneto region and to perform a case-by-case review of a few conditions of interest (febrile and afebrile seizures, ataxia, encephalitis, Guillain-Barré Syndrome, thrombocytopenia, neutropenia and Henoch-Schönlein Purpura). Age and sex differences were also explored. Methods: We identified all reports following MMRV or MMR-V vaccination in the Veneto Region and received into the National Pharmacovigilance Network between 2007 and April 30, 2022. Results: 9,510 reports were retrieved, of which 5,662 (59.5 %) were related to MMRV and 3,848 (40.5 %) to MMR-V. No safety signals were detected supporting the evidence that MMRV and MMR-V vaccinations have a good safety profile. The reporting rate (RR) for serious events between 2007 and 2022 resulted in 13.67 per 10,000 administered doses for MMRV and 10.90 for MMR-V. Conclusion: Passive surveillance data show a significantly higher rate of serious events for males 0-2 years old, both overall and stratified per vaccination strategy. Further studies are needed to confirm this observation. The analyses suggest that retrieved differences do not have a significant impact on the overall safety of both formulations.

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.

Viruses associated with measles-like illnesses in Uganda.

OBJECTIVES: In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and vaccination strategies. METHODS: We used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019. RESULTS: Viral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens. Expected viruses included rubella, human parvovirus B19, Epstein Barr virus, human herpesvirus 6B, human cytomegalovirus, varicella zoster virus and measles virus (detected within the seronegative window-period of infection) and the blood-borne hepatitis B virus. We also detected Saffold virus, human parvovirus type 4, the human adenovirus C2 and vaccine-associated poliovirus type 1. CONCLUSIONS: The study highlights the presence of undiagnosed viruses causing MLI in Uganda, including vaccine-preventable illnesses. NGS can be used to monitor common viral infections at a population level, especially in regions where such infections are prevalent, including low and middle income countries to guide vaccination policy and optimize diagnostic assays.

Insights into measles virus: Serological surveillance and molecular characterization.

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.

Impact of nutritional status on vaccine-induced immunity in children living in South Africa: Investigating the B-cell repertoire and metabolic hormones.

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.

Age-specific prevalence of IgG against measles/rubella and the impact of routine and supplementary immunization activities - a multistage random cluster sampling study with mathematical modelling.

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 2,091 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 post-vaccination 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.

Measles in Czech population with varying vaccination rates in 2018-2019: clinical and laboratory differences between vaccinated and unvaccinated individuals and their relevance to clinical practice.

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.

Detection of intrathecal IgG antibody for varicella and measles diagnosis by evaluation and comparison of a commercial IgG chemiluminescent immunoassay with two ELISAs.

OBJECTIVES: Analyse alternative methods of intrathecal antibody detection by comparing chemiluminescent immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) techniques to determine if CLIA can replace ELISA in the diagnosis of CNS infections. METHODS: A panel of 280 paired samples-cerebrospinal fluid (CSF) and serum-with known antibody reactivities (Varicella, n = 60; Measles, n = 120) and negative samples (n = 100) were used to evaluate the performance of six serological test kits (Enzygnost, VirClia®, and Serion ELISA (Measles and Variella). RESULTS: For Measles virus IgG, the VirClia® IgG monotest revealed 97% and 94% positive and negative agreement to the Enzygnost as reference test, respectively. In contrast, Serion ELISA kits yielded values of 18% and 90%. For the Varicella Zoster virus (VZV) IgG, the VirClia® IgG monotest showed 97% and 90% positive and negative agreement compared to Enzygnost. The Serion ELISA kits showed values of 55% and 86%, respectively. ROC analysis revealed that the areas under the curve for Measles and VZV IgGs were 0.7 and 0.852, respectively, using the Serion kit, and 0.963 and 0.955, for Vircell S.L CLIA technique. VirClia® monotest values were calculated using an antibody index cut-off of 1.3. CONCLUSION: The findings indicate that CLIA testing can improve antibody detection in CSF samples, aiding the diagnosis of infectious neurological impairments.

Early B cell transcriptomic markers of measles-specific humoral immunity following a 3rd dose of MMR vaccine.

B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal study in 232 healthy adult participants before/after a 3rd dose of MMR (MMR3) vaccine. We assessed baseline and early transcriptional patterns in purified B cells and their association with measles-specific humoral immunity after MMR vaccination using two analytical methods ("per gene" linear models and joint analysis). Our study identified distinct early transcriptional signatures/genes following MMR3 that were associated with measles-specific neutralizing antibody titer and/or binding antibody titer. The most significant genes included: the interleukin 20 receptor subunit beta/IL20RB gene (a subunit receptor for IL-24, a cytokine involved in the germinal center B cell maturation/response); the phorbol-12-myristate-13-acetate-induced protein 1/PMAIP1, the brain expressed X-linked 2/BEX2 gene and the B cell Fas apoptotic inhibitory molecule/FAIM, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as IL16 (encoding the B lymphocyte-derived IL-16 ligand of CD4), involved in the crosstalk between B cells, dendritic cells and helper T cells. Significantly enriched pathways included B cell signaling, apoptosis/regulation of apoptosis, metabolic pathways, cell cycle-related pathways, and pathways associated with viral infections, among others. In conclusion, our study identified genes/pathways linked to antigen-induced B cell proliferation, differentiation, apoptosis, and clonal selection, that are associated with, and impact measles virus-specific humoral immunity after MMR vaccination.

Assessment of using Google Trends for real-time monitoring of infectious disease outbreaks: a measles case study.

Measles remains a significant threat to children worldwide despite the availability of effective vaccines. The COVID-19 pandemic exacerbated the situation by leading to the postponement of supplementary measles immunization activities. Along with this postponement, measles surveillance also deteriorated, with the lowest number of submitted specimens in over a decade. In this study, we focus on measles as a challenging case study due to its high vaccination coverage, which leads to smaller outbreaks and potentially weaker signals on Google Trends. Our research aimed to explore the feasibility of using Google Trends for real-time monitoring of infectious disease outbreaks. We evaluated the correlation between Google Trends searches and clinical case data using the Pearson correlation coefficient and Spearman's rank correlation coefficient across 30 European countries and Japan. The results revealed that Google Trends was most suitable for monitoring acute disease outbreaks at the regional level in high-income countries, even when there are only a few weekly cases. For example, from 2017 to 2019, the Pearson correlation coefficient was 0.86 (p-value< 0.05) at the prefecture level for Okinawa, Japan, versus 0.33 (p-value< 0.05) at the national level for Japan. Furthermore, we found that the Pearson correlation coefficient may be more suitable than Spearman's rank correlation coefficient for evaluating the correlations between Google Trends search data and clinical case data. This study highlighted the potential of utilizing Google Trends as a valuable tool for timely public health interventions to respond to infectious disease outbreaks, even in the context of diseases with high vaccine coverage.