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Journal of Molecular Biology Jul 2023Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major... (Review)
Review
Vaccines are among the greatest tools for prevention and control of disease. They have eliminated smallpox from the planet, decreased morbidity and mortality for major infectious diseases like polio, measles, mumps, and rubella, significantly blunted the impact of the COVID-19 pandemic, and prevented viral induced cancers such as cervical cancer caused by human papillomavirus. Recent technological advances, in genomics, structural biology, and human immunology have transformed vaccine development, enabling new technologies such as mRNA vaccines to greatly accelerate development of new and improved vaccines. In this review, we briefly highlight the history of vaccine development, and provide examples of where advances in genomics and structural biology, paved the way for development of vaccines for bacterial and viral diseases.
Topics: Humans; COVID-19; Molecular Biology; Pandemics; Virus Diseases; Viral Vaccines
PubMed: 37080423
DOI: 10.1016/j.jmb.2023.168113 -
Vaccine Oct 2023Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date,...
Chikungunya virus (CHIKV) is an alphavirus transmitted by mosquitos that causes a debilitating disease characterized by fever and long-lasting polyarthralgia. To date, no vaccine has been licensed, but multiple vaccine candidates are under evaluation in clinical trials. One of these vaccines is based on a measles virus vector encoding for the CHIKV structural genes C, E3, E2, 6K, and E1 (MV-CHIK), which proved safe in phase I and II clinical trials and elicited CHIKV-specific antibody responses in adult measles seropositive vaccine recipients. Here, we predicted T-cell epitopes in the CHIKV structural genes and investigated whether MV-CHIK vaccination induced CHIKV-specific CD4 and/or CD8 T-cell responses. Immune-dominant regions containing multiple epitopes in silico predicted to bind to HLA class II molecules were found for four of the five structural proteins, while no such regions were predicted for HLA class I. Experimentally, CHIKV-specific CD4 T-cells were detected in six out of twelve participants after a single MV-CHIK vaccination and more robust responses were found 4 weeks after two vaccinations (ten out of twelve participants). T-cells were mainly directed against the three large structural proteins C, E2 and E1. Next, we sorted and expanded CHIKV-specific T cell clones (TCC) and identified human CHIKV T-cell epitopes by deconvolution. Interestingly, eight out of nine CD4 TCC recognized an epitope in accordance with the in silico prediction. CHIKV-specific CD8 T-cells induced by MV-CHIK vaccination were inconsistently detected. Our data show that the MV-CHIK vector vaccine induced a functional transgene-specific CD4 T cell response which, together with the evidence of neutralizing antibodies as correlate of protection for CHIKV, makes MV-CHIK a promising vaccine candidate in the prevention of chikungunya.
Topics: Adult; Humans; Antibodies, Neutralizing; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Chikungunya Fever; Chikungunya virus; Epitopes, T-Lymphocyte; Measles Vaccine; Measles virus; Viral Vaccines
PubMed: 37726181
DOI: 10.1016/j.vaccine.2023.09.022 -
Global genetic diversity of measles virus (Paramyxoviridae: ): historical aspects and current state.Voprosy Virusologii Nov 2023Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological... (Review)
Review
Monitoring the circulation of the measles virus and studying its genetic diversity is an important component of the measles elimination program. A methodological approach to molecular genetic studies and their interpretation in the measles surveillance was developed in the early 2000s. During its development, clear areas of circulation of each genotype of the virus were identified, therefore, the determination of viruses' genotypes was proposed to monitor circulation and identify transmission pathways. However, in the future, due to a significant decrease in the number of active genotypes, an approach based on sub-genotyping was proposed: determining not only the genotype of the virus, but also its genetic lineage/genetic variant. The Global Measles and Rubella Laboratory Network (GMRLN) systematically monitors the circulation of the measles virus at the sub-genotypic level, depositing the results in a specialized database MeaNS2. It is this database that is the most complete and reliable source of information about the genetic characteristic of measles viruses. This review presents both historical information and the latest data on the global genetic diversity of the measles virus.
Topics: Humans; Measles virus; Morbillivirus; Paramyxoviridae; Molecular Epidemiology; Measles; Genotype; Genetic Variation
PubMed: 38156571
DOI: 10.36233/0507-4088-187 -
Healthcare (Basel, Switzerland) Dec 2023A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental... (Review)
Review
A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. Specific microbes that have been associated or potentially associated with at least one of these conditions include , , , Borna disease virus, (Lyme disease), , , coronaviruses (e.g., SARS-CoV-2), , cytomegalovirus, enteroviruses, Epstein-Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, , , rubella virus, Group A (PANDAS), , , (syphilis), , and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.
PubMed: 38200989
DOI: 10.3390/healthcare12010083 -
Experimental Neurology Jul 2023Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques,... (Review)
Review
Microphysiological systems (MPS) are 2D or 3D multicellular constructs able to mimic tissue microenvironments. The latest models encompass a range of techniques, including co-culturing of various cell types, utilization of scaffolds and extracellular matrix materials, perfusion systems, 3D culture methods, 3D bioprinting, organ-on-a-chip technology, and examination of tissue structures. Several human brain 3D cultures or brain MPS (BMPS) have emerged in the last decade. These organoids or spheroids are 3D culture systems derived from induced pluripotent cells or embryonic stem cells that contain neuronal and glial populations and recapitulate structural and physiological aspects of the human brain. BMPS have been introduced recently in the study and modeling of neuroinfectious diseases and have proven to be useful in establishing neurotropism of viral infections, cell-pathogen interactions needed for infection, assessing cytopathological effects, genomic and proteomic profiles, and screening therapeutic compounds. Here we review the different methodologies of organoids used in neuroinfectious diseases including spheroids, guided and unguided protocols as well as microglia and blood-brain barrier containing models, their specific applications, and limitations. The review provides an overview of the models existing for specific infections including Zika, Dengue, JC virus, Japanese encephalitis, measles, herpes, SARS-CoV2, and influenza viruses among others, and provide useful concepts in the modeling of disease and antiviral agent screening.
Topics: Humans; Microphysiological Systems; Proteomics; RNA, Viral; COVID-19; SARS-CoV-2; Brain; Zika Virus; Zika Virus Infection; Induced Pluripotent Stem Cells
PubMed: 37061175
DOI: 10.1016/j.expneurol.2023.114409 -
Virus Evolution 2023In the future, zoonotic spillover events are expected to occur more frequently. Consequences of such events have clearly been demonstrated by recent outbreaks of...
In the future, zoonotic spillover events are expected to occur more frequently. Consequences of such events have clearly been demonstrated by recent outbreaks of monkeypox, Ebola virus, and the well-known severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Virus discovery has proven to be an important tool in the preparation against viral outbreaks, generating data concerning the diversity, quantity, and ecology of the vertebrate virome. Orthoparamyxoviruses, a subfamily within the Paramyxoviridae, are important biosurveillance targets, since they include several known animal, human, and zoonotic pathogens such as Nipah virus, measles virus, and Hendra virus. During this study, 127 bat samples, thirty-four rodent samples, and seventeen shrew samples originating from Belgium were screened for orthoparamyxovirus presence using nested reverse transcription-polymerase chain reaction assays and nanopore sequencing. We present here the complete genomes of six putative new viral species, belonging to the genera and . Characterization of these genomes revealed significant differences in gene composition and organization, both within viruses of the same genus and between viruses of different genera. Remarkably, a previously undetected gene coding for a protein of unknown function was identified in the genome of a putative new . Additionally, phylogenetic analysis of jeilongviruses and henipaviruses reveals a division of both genera into two clades, one consisting of bat-borne viruses and the other consisting of rodent- and shrew-borne viruses, elucidating the need for proper reclassification.
PubMed: 38034864
DOI: 10.1093/ve/vead065 -
One Health (Amsterdam, Netherlands) Dec 2023Measles infections can cause significant morbidity and mortality in human and monkey populations. The endemicity of measles in human populations and viral circulation...
Measles infections can cause significant morbidity and mortality in human and monkey populations. The endemicity of measles in human populations and viral circulation within populations of free-living monkeys may have important repercussions for potential zoonotic transmission events and for the long-term health of monkey populations. Yet, there has not yet been a rigorous investigation of the dynamics of measles transmission where human and monkey populations coexist. In this study, to determine the difference in seroprevalence of the measles virus across different contexts of human-monkey contact, we analyzed serum samples collected from 56 apparently healthy monkeys who occupied diverse contexts, with different degrees of human-monkey contact, in Bangladesh. This is the first report of measles virus seroprevalence in monkeys in Bangladesh. We found a clear association between measles virus seropositivity in monkeys and the context in which they interact with humans. Seroprevalence was the lowest in wild areas (0.0%) and increased in shrines (4.8%), urban areas (5.9%), and was highest among monkeys who are used as performance animals (50.0%). This work suggests that a One Health approach informed by local interspecies transmission dynamics is necessary to develop strategies that both improve measles vaccination coverage, achieve long-term surveillance in monkey populations, and prevent measles spillback to monkeys. This approach aims to inform conservation efforts and protect the long-term health of human and monkey populations.
PubMed: 37332882
DOI: 10.1016/j.onehlt.2023.100571 -
Methods in Molecular Biology (Clifton,... 2024The plaque reduction neutralization test (PRNT) and the enzyme-linked immunosorbent assay (ELISA) are both widely used to assess immunity to infectious diseases such as...
The plaque reduction neutralization test (PRNT) and the enzyme-linked immunosorbent assay (ELISA) are both widely used to assess immunity to infectious diseases such as measles, but they use two different measurement principles: ELISA measures the ability of antibodies to bind to virus components, while the PRNT detects the aptitude of antibodies to prevent the infection of a susceptible cell. As a result, detection of measles virus (MV) neutralizing antibodies is the gold standard for assessing immunity to measles. However, the assay is laborious and requires experience and excellent technical skills. In addition, the result is only available after several days. Therefore, the classical PRNT is not suitable for high-throughput testing. By using an immunocolorimetric assay (ICA) to detect MV-infected cells, the standard PRNT has been developed into a focus reduction neutralization test (FRNT). This assay is faster and has improved specificity. The FRNT described here is extremely useful when immunity to measles virus needs to be assessed in patients with a specific medical condition, such as immunocompromised individuals in whom presumed residual immunity needs to be assessed. The FRNT is not generally recommended for use with large numbers of specimens, such as in a seroprevalence study.
Topics: Neutralization Tests; Measles virus; Measles; Humans; Antibodies, Neutralizing; Antibodies, Viral; Chlorocebus aethiops; Animals; Vero Cells; Viral Plaque Assay; Enzyme-Linked Immunosorbent Assay
PubMed: 38743373
DOI: 10.1007/978-1-0716-3870-5_16 -
Transplantation Oct 2023Updating live vaccines such as measles, mumps, rubella, and varicella (MMRV) is an important step in preparing patients for solid organ transplant (SOT) to prevent...
BACKGROUND
Updating live vaccines such as measles, mumps, rubella, and varicella (MMRV) is an important step in preparing patients for solid organ transplant (SOT) to prevent morbidity from these preventable diseases. However, data for this approach are scarce. Thus, we aimed to describe the seroprevalence of MMRV and the efficacy of the vaccines in our transplant center.
METHODS
Pre-SOT candidates >18 y of age were retrospectively retrieved from SOT database in Memorial Hermann Hospital Texas Medical Center. MMRV serologies are routinely screened at the time of pretransplant evaluation. We divided patients into 2 groups: MMRV-positive group versus MMRV-negative group, patients with positive all MMRV serologies and with negative immunity to at least 1 dose of MMRV, respectively.
RESULTS
A total of 1213 patients were identified. Three hundred ninety-four patients (32.4%) did not have immunity to at least 1 dose of MMRV. Multivariate analysis was conducted. Older age (odds ratio [OR]: 1.04) and liver transplant candidates (OR: 1.71) were associated with seropositivity. Previous history of SOT (OR: 0.54) and pancreas/kidney transplant candidates (OR: 0.24) were associated with seronegativity. Among 394 MMRV seronegative patients, 60 patients received 1 dose of MMR vaccine and 14 patients received 1 dose of varicella-zoster virus vaccine without severe adverse events. A total of 35% (13/37) of patients who had follow-up serologies did not have a serological response.
CONCLUSIONS
A significant number of pre-SOT candidates were not immune to at least 1 dose of MMRV. This highlights the importance of MMRV screening and vaccinations pre-SOT. Postvaccination serological confirmation should be performed to evaluate the necessity for a second dose.
Topics: Humans; Adult; Infant; Herpesvirus 3, Human; Mumps; Seroepidemiologic Studies; Retrospective Studies; Vaccines, Combined; Measles; Rubella; Chickenpox Vaccine; Chickenpox; Vaccination; Organ Transplantation; Antibodies, Viral
PubMed: 37309028
DOI: 10.1097/TP.0000000000004681 -
JAMA Network Open Oct 2023Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine...
IMPORTANCE
Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions.
OBJECTIVE
To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols.
EXPOSURES
Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine.
MAIN OUTCOME AND MEASURE
Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis.
RESULTS
The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination.
CONCLUSIONS AND RELEVANCE
The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.
Topics: Child; Humans; Child, Preschool; Adolescent; Viral Vaccines; Chickenpox; Chickenpox Vaccine; Mumps; Vaccines, Combined; Transplant Recipients; Cohort Studies; Rubella; Measles; Vaccines, Attenuated
PubMed: 37824141
DOI: 10.1001/jamanetworkopen.2023.37602