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Pediatrics Mar 2024The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and...
The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 25 to 26, 2023, to discuss meningococcal vaccines, mpox vaccines, respiratory syncytial virus (RSV) vaccines, influenza vaccines, coronavirus disease 2019 (COVID-19) vaccines, and the combined pediatric and adult immunization schedules for 2024. The ACIP also held special meetings on September 12 and September 22 to discuss COVID-19 2023-2024 vaccine recommendations and RSV immunization in pregnant women. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include recommendations for XBB monovalent COVID-19 immunization for the 2023-2024 respiratory season, the recently licensed pentavalent meningococcal conjugate vaccine and mpox vaccination in high-risk young adults, and discussion regarding the parallel strategies of protection against RSV disease in infants via maternal immunization during pregnancy or direct prophylaxis of infants with nirsevimab.
Topics: Infant; Young Adult; Child; Humans; Female; Pregnancy; Meningococcal Vaccines; Influenza, Human; Advisory Committees; Respiratory Syncytial Viruses; COVID-19; Immunization; Neisseria meningitidis
PubMed: 38095041
DOI: 10.1542/peds.2023-064990 -
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 Aug 2023Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of quadrivalent meningococcal polysaccharide vaccine (MPV ACYW135) compared with quadrivalent meningococcal conjugate vaccine (Menactra®) in Malian children.
Affordable, polyvalent meningococcal vaccines are needed for use in emergency reactive immunization campaigns. A phase IV randomized, observer-blind, controlled study compared the safety and immunogenicity of a quadrivalent meningococcal polysaccharide vaccine (MPV-4, MPV ACYW135) and quadrivalent meningococcal ACWY conjugate vaccine (MCV-4, Menactra®). Healthy, 2- to 10-year-old children in Bamako, Mali, were randomized 1:1 to receive one dose of MPV-4 or MCV-4. Safety outcomes were evaluated for 6 months post-immunization. Immunogenicity for all serogroups was assessed for non-inferiority between MPV-4 and MCV-4 30 days post immunization by serum bactericidal antibody assay using baby rabbit complement (rSBA). From December 2020 to July 2021, 260 healthy subjects were consented and randomized. At Day 30 post-immunization, the proportions of subjects with rSBA titers ≥ 128 for all serogroups in the MPV-4 group were non-inferior to those in MCV-4 group. The proportions of subjects with rSBA ≥ 4-fold increase and rSBA titers ≥ 8 for all serogroups were similar among vaccine groups ( > .05). Geometric Mean Titers and Geometric Mean Fold Increases for all serogroups in both vaccine groups were similar ( > .05). Few local and systemic post-immunization reactions of similar severity and duration were observed within 7 days and were similar in both groups ( > .05). All resolved without sequelae. Unsolicited adverse events were similar in both groups regarding relationship to study vaccine, severity and duration. No serious adverse events were reported during the study period. MPV ACYW135 showed a non-inferior immunogenicity profile and a comparable reactogenicity profile to MCV-4 in Malian children aged 2-10 years.: NCT04450498.
Topics: Humans; Meningococcal Vaccines; Vaccines, Conjugate; Neisseria meningitidis; Vaccination; Serogroup; Antibodies, Bacterial; Meningococcal Infections
PubMed: 37401618
DOI: 10.1080/21645515.2023.2230829 -
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 -
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 -
Microorganisms Dec 2023Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this...
BACKGROUND
Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response.
METHODS
A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination.
RESULTS
There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration.
CONCLUSIONS
CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.
PubMed: 38257857
DOI: 10.3390/microorganisms12010030