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Frontiers in Immunology 2024B cell transcriptomic signatures hold promise for the early prediction of vaccine-induced humoral immunity and vaccine protective efficacy. We performed a longitudinal...
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 3 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/ 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/, the brain expressed X-linked 2/ gene and the B cell Fas apoptotic inhibitory molecule/, involved in the selection of high-affinity B cell clones and apoptosis/regulation of apoptosis; as well as (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.
Topics: Adult; Humans; Measles-Mumps-Rubella Vaccine; Immunity, Humoral; Longitudinal Studies; Antibodies, Viral; Measles; Gene Expression Profiling; Nerve Tissue Proteins
PubMed: 38633249
DOI: 10.3389/fimmu.2024.1358477 -
MMWR. Morbidity and Mortality Weekly... Apr 2024Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S....
Measles is a highly infectious febrile rash illness and was declared eliminated in the United States in 2000. However, measles importations continue to occur, and U.S. measles elimination status was threatened in 2019 as the result of two prolonged outbreaks among undervaccinated communities in New York and New York City. To assess U.S. measles elimination status after the 2019 outbreaks and to provide context to understand more recent increases in measles cases, CDC analyzed epidemiologic and laboratory surveillance data and the performance of the U.S. measles surveillance system after these outbreaks. During January 1, 2020-March 28, 2024, CDC was notified of 338 confirmed measles cases; 97 (29%) of these cases occurred during the first quarter of 2024, representing a more than seventeenfold increase over the mean number of cases reported during the first quarter of 2020-2023. Among the 338 reported cases, the median patient age was 3 years (range = 0-64 years); 309 (91%) patients were unvaccinated or had unknown vaccination status, and 336 case investigations included information on ≥80% of critical surveillance indicators. During 2020-2023, the longest transmission chain lasted 63 days. As of the end of 2023, because of the absence of sustained measles virus transmission for 12 consecutive months in the presence of a well-performing surveillance system, U.S. measles elimination status was maintained. Risk for widespread U.S. measles transmission remains low because of high population immunity. However, because of the increase in cases during the first quarter of 2024, additional activities are needed to increase U.S. routine measles, mumps, and rubella vaccination coverage, especially among close-knit and undervaccinated communities. These activities include encouraging vaccination before international travel and rapidly investigating suspected measles cases.
Topics: United States; Humans; Infant; Infant, Newborn; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Measles; Measles virus; Vaccination; Vaccination Coverage; Disease Outbreaks; New York City; Measles-Mumps-Rubella Vaccine
PubMed: 38602886
DOI: 10.15585/mmwr.mm7314a1 -
Human Vaccines & Immunotherapeutics Dec 2024The 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...
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 ( < .001). At 12 months, the measles antibodies and seropositive rate in the infants who received MCV vaccination increased sharply ( < .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, = .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.
Topics: Infant; Humans; Infant, Newborn; Infant, Premature; Measles Vaccine; Measles; Measles virus; Antibodies, Viral; China; Vaccination
PubMed: 38599768
DOI: 10.1080/21645515.2024.2338505 -
Indian Pediatrics Apr 2024Mumps is a global public health problem caused by mumps virus, a member of paramyxoviridae family. MMR (Mumps, Measles, Rubella), an effective vaccine, has been... (Review)
Review
Mumps is a global public health problem caused by mumps virus, a member of paramyxoviridae family. MMR (Mumps, Measles, Rubella), an effective vaccine, has been incorporated into routine immunization schedules in over 100 countries. On the contrary, in India, vaccine against mumps has not been included in the routine immunization schedule as mumps is still not viewed as a significant public health problem by the government to warrant such an intervention. An increasing number of mumps outbreaks being reported from many parts of the country in the recent past, is matter of concern. The current paper reviews the situation of mumps in India including the recent surge, and discusses the remedial measures to contain these outbreaks. We conclude that inclusion of Mumps component as MMR vaccine in the Universal Immunization Programme of India along with strengthening surveillance is required to tackle the situation.
Topics: Humans; Antibodies, Viral; India; Measles; Measles-Mumps-Rubella Vaccine; Mumps; Rubella
PubMed: 38597102
DOI: No ID Found -
The Journal of Infection May 2024In 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...
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.
Topics: Humans; Uganda; Child, Preschool; Measles; Infant; Child; High-Throughput Nucleotide Sequencing; Male; Female; Adolescent; Viruses; Genome, Viral; Adult; Young Adult; Virus Diseases; Metagenomics; Measles virus
PubMed: 38588959
DOI: 10.1016/j.jinf.2024.106148 -
BioRxiv : the Preprint Server For... Mar 2024Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that...
Immunoglobulin (IGH, IGK, IGL) loci in the human genome are highly polymorphic regions that encode the building blocks of the light and heavy chain IG proteins that dimerize to form antibodies. The processes of V(D)J recombination and somatic hypermutation in B cells are responsible for creating an enormous reservoir of highly specific antibodies capable of binding a vast array of possible antigens. However, the antibody repertoire is fundamentally limited by the set of variable (V), diversity (D), and joining (J) alleles present in the germline IG loci. To better understand how the germline IG haplotypes contribute to the expressed antibody repertoire, we combined genome sequencing of the germline IG loci with single-cell transcriptome sequencing of B cells from the same donor. Sequencing and assembly of the germline IG loci captured the IGH locus in a single fully-phased contig where the maternal and paternal contributions to the germline V, D, and J repertoire can be fully resolved. The B cells were collected following a measles, mumps, and rubella (MMR) vaccination, resulting in a population of cells that were activated in response to this specific immune challenge. Single-cell, full-length transcriptome sequencing of these B cells resulted in whole transcriptome characterization of each cell, as well as highly-accurate consensus sequences for the somatically rearranged and hypermutated light and heavy chain IG transcripts. A subset of antibodies synthesized based on their consensus heavy and light chain transcript sequences demonstrated binding to measles antigens and neutralization of measles live virus.
PubMed: 38585716
DOI: 10.1101/2024.03.26.586834 -
Emerging Infectious Diseases May 2024We investigated clinically suspected measles cases that had discrepant real-time reverse transcription PCR (rRT-PCR) and measles-specific IgM test results to determine...
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.
Topics: Humans; Immunoglobulin M; Measles; Antibodies, Viral; Japan; Child; Child, Preschool; Measles virus; Male; Adult; Female; Infant; Adolescent; Immunoglobulin G; Reverse Transcriptase Polymerase Chain Reaction; Measles Vaccine; Young Adult; Real-Time Polymerase Chain Reaction
PubMed: 38579738
DOI: 10.3201/eid3005.231757 -
Cureus Mar 2024Medical education is the foundation of knowledge among medical students. This study aims to investigate the knowledge of 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.
PubMed: 38576644
DOI: 10.7759/cureus.55572 -
Journal of Virology May 2024In 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...
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.
Topics: Animals; Female; Humans; Mice; Antibodies, Neutralizing; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Disease Models, Animal; Genetic Vectors; Measles Vaccine; Measles virus; Mice, Inbred BALB C; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 38563763
DOI: 10.1128/jvi.01693-23 -
Journal of Virology May 2024Severe 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...
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.
Topics: Animals; Spike Glycoprotein, Coronavirus; Chlorocebus aethiops; SARS-CoV-2; COVID-19; Measles virus; COVID-19 Vaccines; Humans; Antibodies, Viral; Antibodies, Neutralizing; Genetic Vectors; Vero Cells; Pandemics; Female; Betacoronavirus; Pneumonia, Viral; Coronavirus Infections; Viral Vaccines; Disease Models, Animal
PubMed: 38563762
DOI: 10.1128/jvi.01762-23