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The Journal of Clinical Investigation Aug 2023BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have... (Clinical Trial)
Clinical Trial
BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on the surface Vi-capsular polysaccharide of S. Typhi; these include a plain-polysaccharide-based vaccine, ViPS, and a glycoconjugate vaccine, ViTT. To understand immune responses to these vaccines and their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial, who were then challenged with S. Typhi in a controlled human infection model (CHIM). These data were used to conduct differential gene expression analyses, gene set and modular analyses, B cell repertoire analyses, and time-course analyses at various post-vaccination and post-challenge time points between participants receiving ViTT, ViPS, or a control meningococcal vaccine.RESULTSTranscriptomic responses revealed strong differential molecular signatures between the 2 typhoid vaccines, mostly driven by the upregulation in humoral immune signatures, including selective usage of immunoglobulin heavy chain variable region (IGHV) genes and more polarized clonal expansions. We describe several molecular correlates of protection against S. Typhi infection, including clusters of B cell receptor (BCR) clonotypes associated with protection, with known binders of Vi-polysaccharide among these.CONCLUSIONThe study reports a series of contemporary analyses that reveal the transcriptomic signatures after vaccination and infectious challenge, while identifying molecular correlates of protection that may inform future vaccine design and assessment.TRIAL REGISTRATIONClinicalTrials.gov NCT02324751.
Topics: Adult; Humans; Polysaccharides, Bacterial; Receptors, Antigen, B-Cell; Salmonella typhi; Typhoid Fever; Typhoid-Paratyphoid Vaccines; Vaccination
PubMed: 37402153
DOI: 10.1172/JCI169676 -
Journal of Molecular Biology Dec 2023The history of DNA vaccine began as early as the 1960s with the discovery that naked DNA can transfect mammalian cells in vivo. In 1992, the evidence that such... (Review)
Review
The history of DNA vaccine began as early as the 1960s with the discovery that naked DNA can transfect mammalian cells in vivo. In 1992, the evidence that such transfection could lead to the generation of antigen-specific antibody responses was obtained and supported the development of this technology as a novel vaccine platform. The technology then attracted immense interest and high hopes in vaccinology, as evidence of high immunogenicity and protection against virulent challenges accumulated from several animal models for several diseases. In particular, the capacity to induce T-cell responses was unprecedented in non-live vaccines. However, the technology suffered its major knock when the success in animals failed to translate to humans, where DNA vaccine candidates were shown to be safe but remained poorly immunogenic, or not associated with clinical benefit. Thanks to a thorough exploration of the molecular mechanisms of action of these vaccines, an impressive range of approaches have been and are currently being explored to overcome this major challenge. Despite limited success so far in humans as compared with later genetic vaccine technologies such as viral vectors and mRNA, DNA vaccines are not yet optimised for human use and may still realise their potential.
Topics: Animals; Humans; Genetic Vectors; T-Lymphocytes; Vaccines, DNA
PubMed: 37797831
DOI: 10.1016/j.jmb.2023.168297 -
Microorganisms Dec 2023is commensal of the human pharynx and occasionally invades the host, causing the life-threatening illness invasive meningococcal disease. The meningococcus is a highly... (Review)
Review
is commensal of the human pharynx and occasionally invades the host, causing the life-threatening illness invasive meningococcal disease. The meningococcus is a highly diverse and adaptable organism thanks to natural competence, a propensity for recombination, and a highly repetitive genome. These mechanisms together result in a high level of antigenic variation to invade diverse human hosts and evade their innate and adaptive immune responses. This review explores the ways in which this diversity contributes to the evolutionary history and population structure of the meningococcus, with a particular focus on microevolution. It examines studies on meningococcal microevolution in the context of within-host evolution and persistent carriage; microevolution in the context of meningococcal outbreaks and epidemics; and the potential of microevolution to contribute to antimicrobial resistance and vaccine escape. A persistent theme is the idea that the process of microevolution contributes to the development of new hyperinvasive meningococcal variants. As such, microevolution in this species has significant potential to drive future public health threats in the form of hypervirulent, antibiotic-resistant, vaccine-escape variants. The implications of this on current vaccination strategies are explored.
PubMed: 38138149
DOI: 10.3390/microorganisms11123005 -
Cureus Nov 2023In healthy people, (the meningococcus) is a typical component of the nasopharyngeal microbiome, but in those who are susceptible, it can cause septicemia and... (Review)
Review
In healthy people, (the meningococcus) is a typical component of the nasopharyngeal microbiome, but in those who are susceptible, it can cause septicemia and meningitis. This section gives a general overview of the meningococcus types and the sickness induced by Evaluate genes for phase-changeable adhesions, virulence factors, and effective colonization of the human host. In our final section, we summarize the evolution of meningococcal vaccines and their current state while emphasizing the value of ongoing molecular research into the pathogen's epidemiology and structural analysis of its antigens. IMD is a major global source of morbidity and mortality and a public health concern. IMD can manifest as an epidemic with breakouts or as an endemic illness with sporadic instances. There are 13 serogroups of Neisseria meningitis strains, however, only five (A, B, C, W-135, and Y) account for the majority of IMD globally. IMD poses a risk to people of all ages, although young children and teenagers are especially at risk. Meningitis and septicemia are the two clinical symptoms of IMD that occur most frequently, while both clinical presentations can occasionally exist. Age might affect the clinical pattern; in early childhood, the clinical manifestations could be more subtle, and the diagnosis may be trickier than in older kids or teenagers. In 4.3-11.2% of instances, there are sequelae, and death occurs in 6-10% of cases. Although vaccination remains the most effective method of preventing meningococcal disease, it is crucial to identify children with meningococcal infection as soon as possible to begin systemic antibiotic therapy. The prevalence of the disease has decreased as a result of the recent introduction of various meningococcal vaccinations on a global scale. Increasing meningococcal disease vaccination rates, keeping an eye on IMD, and creating a special vaccine that can protect against all of the major meningococcal strains should be the priorities for the upcoming few years.
PubMed: 38073961
DOI: 10.7759/cureus.48509 -
Human Vaccines & Immunotherapeutics Dec 2023This review reports on the recent epidemiology of invasive meningococcal disease (IMD) within the Gulf Cooperation Council (GCC) Countries (focusing from 2012 onwards),... (Review)
Review
This review reports on the recent epidemiology of invasive meningococcal disease (IMD) within the Gulf Cooperation Council (GCC) Countries (focusing from 2012 onwards), the existing immunization strategies and the potential for IMD resurgence. MenACWY vaccination is now established in infant or adolescent immunization programs in Saudi Arabia, Bahrain, Kuwait, and the United Arab Emirates. At present, GCC Countries do not include MenB immunization. National health surveillance reports indicate a total of 156 IMD cases reported across the GCC Countries between 2012 and 2021; between 30% and 80% of cases were reported in individuals aged ≥15 years. Lack of serogroup data hinders the assessment of vaccine impact and decision-making on additional vaccine introductions (e.g. MenB immunization). Hajj/Umrah pilgrimage and the increasing number of large-scale commercial and social events held in the GCC Countries pose a potential risk for future IMD outbreaks. Immunization policies for such events could be strengthened.
Topics: Infant; Adolescent; Humans; Meningococcal Infections; Saudi Arabia; Disease Outbreaks; United Arab Emirates; Vaccination; Meningococcal Vaccines
PubMed: 37051899
DOI: 10.1080/21645515.2023.2193120 -
Trends in Microbiology Aug 2023Neisseria meningitidis is a human-adapted pathogen that causes meningitis and sepsis worldwide. N. meningitidis factor H-binding protein (fHbp) provides a mechanism for... (Review)
Review
Neisseria meningitidis is a human-adapted pathogen that causes meningitis and sepsis worldwide. N. meningitidis factor H-binding protein (fHbp) provides a mechanism for immune evasion by binding human complement factor H (CFH) to protect it from complement-mediated killing. Here, we discuss features of fHbp which enable it to engage human CFH (hCFH), and the regulation of fHbp expression. Studies of host susceptibility and bacterial genome-wide association studies (GWAS) highlight the importance of the interaction between fHbp and CFH and other complement factors, such as CFHR3, on the development of invasive meningococcal disease (IMD). Understanding the basis of fHbp:CFH interactions has also informed the design of next-generation vaccines as fHbp is a protective antigen. Structure-informed refinement of fHbp vaccines will help to combat the threat posed by the meningococcus, and accelerate the elimination of IMD.
Topics: Humans; Complement Factor H; Bacterial Proteins; Antigens, Bacterial; Virulence; Carrier Proteins; Genome-Wide Association Study; Disease Susceptibility; Neisseria meningitidis; Meningococcal Infections; Meningococcal Vaccines; Bacterial Vaccines
PubMed: 36941192
DOI: 10.1016/j.tim.2023.02.011 -
Infectious Diseases and Therapy Dec 2023The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19...
The global invasive meningococcal disease (IMD) landscape changed considerably during the COVID-19 pandemic, as evidenced by decreased incidence rates due to COVID-19 mitigation measures, such as limited social contact, physical distancing, mask wearing, and hand washing. Vaccination rates were also lower during the pandemic relative to pre-pandemic levels. Although policymakers may have shifted their focus away from IMD vaccination programs to COVID-19 vaccination programs, strong arguments support implementation and prioritization of IMD vaccination programs; IMD cases have increased in some countries and IMD rates may even have exceeded pre-pandemic levels. Additional concerns include increased susceptibility due to vaccination coverage gaps, increased incidence of other respiratory pathogens, immunity debt from lockdown restrictions, and increased IMD epidemiologic variability. The full range of benefits of widely available and effective meningococcal vaccines needs to be considered, especially in health technology assessments, where the broad benefits of these vaccines are neither accurately quantified nor captured in implementation policy decisions. Importantly, implementation of meningococcal vaccination programs in the current IMD climate also appeals to broader healthcare principles, including preparedness rather than reactive approaches, generally accepted benefit-risk approaches to vaccination, historical precedent, and the World Health Organization's goal of defeating meningitis by 2030. Countries should therefore act swiftly to bolster existing meningococcal vaccination strategies to provide broad coverage across age groups and serogroups given the recent increases in IMD incidence.
PubMed: 38048020
DOI: 10.1007/s40121-023-00888-w -
Human Vaccines & Immunotherapeutics Dec 2023Invasive meningococcal disease (IMD), caused by , is life-threatening with a high case fatality rate (CFR) and severe sequelae. We compiled and critically discussed the... (Review)
Review
Invasive meningococcal disease (IMD), caused by , is life-threatening with a high case fatality rate (CFR) and severe sequelae. We compiled and critically discussed the evidence on IMD epidemiology, antibiotic resistance and disease management in Vietnam, focusing on children. PubMed, Embase and gray literature searches for English, Vietnamese and French publications, with no date restrictions, retrieved 11 eligible studies. IMD incidence rate (/100,000 population) was 7.4 [95% confidence interval 3.6-15.3] in children under 5 years of age; driven by high rates in infants (e.g. 29.1 [8.0-106.0] in 7-11 month-olds). Serogroup B IMD was predominant. strains may have developed resistance to streptomycin, sulfonamides, ciprofloxacin, and possibly ceftriaxone. There was a lack of current data on diagnosis and treatment of IMD, which remain challenging. Healthcare professionals should be trained to rapidly recognize and treat IMD. Preventive measures, such as routine vaccination, could help address the medical need.
Topics: Child; Child, Preschool; Humans; Infant; Incidence; Meningococcal Infections; Meningococcal Vaccines; Neisseria meningitidis; Neisseria meningitidis, Serogroup B; Serogroup; Vietnam
PubMed: 36951161
DOI: 10.1080/21645515.2023.2172922 -
Expert Review of Vaccines 2024The epidemiology of invasive meningococcal disease (IMD), a rare but potentially fatal illness, is typically described as unpredictable and subject to sporadic outbreaks. (Review)
Review
INTRODUCTION
The epidemiology of invasive meningococcal disease (IMD), a rare but potentially fatal illness, is typically described as unpredictable and subject to sporadic outbreaks.
AREAS COVERED
Meningococcal epidemiology and vaccine use during the last ~ 200 years are examined within the context of meningococcal characterization and classification to guide future IMD prevention efforts.
EXPERT OPINION
Historical and contemporary data highlight the dynamic nature of meningococcal epidemiology, with continued emergence of hyperinvasive clones and affected regions. Recent shifts include global increases in serogroup W disease, meningococcal antimicrobial resistance (AMR), and meningococcal urethritis; additionally, unvaccinated populations have experienced disease resurgences following lifting of COVID-19 restrictions. Despite these changes, a close analysis of meningococcal epidemiology indicates consistent dominance of serogroups A, B, C, W, and Y and elevated IMD rates among infants and young children, adolescents/young adults, and older adults. Demonstrably effective vaccines against all 5 major disease-causing serogroups are available, and their prophylactic use represents a powerful weapon against IMD, including AMR. The World Health Organization's goal of defeating meningitis by the year 2030 demands broad protection against IMD, which in turn indicates an urgent need to expand meningococcal vaccination programs across major disease-causing serogroups and age-related risk groups.
Topics: Child; Infant; Adolescent; Young Adult; Humans; Child, Preschool; Aged; Neisseria meningitidis; Meningococcal Infections; Meningococcal Vaccines; Disease Outbreaks; Serogroup; Vaccines, Combined
PubMed: 38517733
DOI: 10.1080/14760584.2024.2329618