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Paediatric Drugs Sep 202320‑valent pneumococcal conjugate vaccine (PCV20; Prevnar 20; Apexxnar) is a pneumococcal conjugate vaccine (PCV) developed by Pfizer for active immunization for the... (Review)
Review
20‑valent pneumococcal conjugate vaccine (PCV20; Prevnar 20; Apexxnar) is a pneumococcal conjugate vaccine (PCV) developed by Pfizer for active immunization for the prevention of pneumococcal infections. PCV20 has a similar structure and formulation to Pfizer's 13-valent PCV (PCV13; Prevnar 13; Prevenar 13), with the addition of polysaccharides to target seven further Streptococcus pneumoniae serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F). PCV20 has been approved for active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae in adults since June 2021 in the USA and since February 2022 in the EU. Following further evaluation of its safety, immunogenicity, and effectiveness in pediatric populations, in April 2023 PCV20 received its first pediatric approval, in the USA, for active immunization for the prevention of invasive pneumococcal disease (IPD) caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks to 17 years of age and for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in individuals 6 weeks to 5 years of age. This article summarizes the milestones in the development of PCV20 leading to this first pediatric approval for active immunization for the prevention of IPD and otitis media caused by S. pneumoniae.
Topics: Adult; Child; Humans; Vaccines, Conjugate; Streptococcus pneumoniae; Pneumococcal Infections; Pneumococcal Vaccines; Vaccination; Otitis Media
PubMed: 37440125
DOI: 10.1007/s40272-023-00584-9 -
International Journal of Molecular... Jul 2023Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of... (Review)
Review
The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.
Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.
Topics: Adult; Humans; Aged; Pneumonia, Pneumococcal; Prevalence; Pneumococcal Infections; Streptococcus pneumoniae; Anti-Bacterial Agents; Macrolides; Community-Acquired Infections; Cardiovascular Diseases
PubMed: 37446214
DOI: 10.3390/ijms241311038 -
Frontiers in Immunology 2023Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by... (Review)
Review
Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by pneumococcal polysaccharide and conjugate vaccines, their limited coverage and the emergence of non-vaccine serotypes have highlighted the need for alternative approaches. Protein-based pneumococcal vaccines, targeting conserved surface proteins of , have emerged as a promising strategy. In this review, we provide an overview of the advancements made in the development of pneumococcal protein vaccines. We discuss the key protein vaccine candidates, highlight their vaccination results in animal studies, and explore the challenges and future directions in protein-based pneumococcal vaccine.
Topics: Animals; Pneumococcal Vaccines; Pneumococcal Infections; Streptococcus pneumoniae; Bacterial Proteins; Vaccines, Conjugate
PubMed: 37818378
DOI: 10.3389/fimmu.2023.1278346 -
Human Vaccines & Immunotherapeutics Dec 2024Like the other invasive encapsulated bacteria, is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive...
Like the other invasive encapsulated bacteria, is also covered with a polysaccharide structure. Infants and elderly are most vulnerable to the invasive and noninvasive diseases caused by . Although antibodies against polysaccharide capsule are efficient in eliminating , the T cell independent nature of the immune response against polysaccharide vaccines renders them weakly antigenic. The introduction of protein conjugated capsular polysaccharide vaccines helped overcome the weak immunogenicity of pneumococcal polysaccharides and decreased the incidence of pneumococcal diseases, especially in pediatric population. Conjugate vaccines elicit T cell dependent response which involve the interaction of specialized CD4+ T cells, called follicular helper T cells (Tfh) with germinal center B cells in secondary lymphoid organs. Despite their improved immunogenicity, conjugate vaccines still need to be administered three to four times in infants during the first 15 month of their life because they mount poor Tfh response. Recent studies revealed fundamental differences in the generation of Tfh cells between neonates and adults. As the portfolio of pneumococcal conjugate vaccines continues to increase, better understanding of the mechanisms of antibody development in different age groups will help in the development of pneumococcal vaccines tailored for different ages.
Topics: Infant; Adult; Infant, Newborn; Child; Humans; Aged; Pneumococcal Vaccines; Streptococcus pneumoniae; Pneumococcal Infections; Vaccines, Conjugate; Antibodies; Polysaccharides; Antibodies, Bacterial
PubMed: 38567485
DOI: 10.1080/21645515.2024.2336358 -
Infectious Diseases Now Nov 2023In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to... (Review)
Review
In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is >0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for.
Topics: Infant; Child; Humans; Infant, Newborn; Meningitis, Pneumococcal; Anti-Bacterial Agents; Streptococcus pneumoniae; Cefotaxime; Communicable Diseases
PubMed: 37741342
DOI: 10.1016/j.idnow.2023.104788 -
Clinical Infectious Diseases : An... Oct 2023Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months... (Randomized Controlled Trial)
Randomized Controlled Trial
A Phase 3, Randomized, Double-Blind, Comparator-Controlled Study to Evaluate Safety, Tolerability, and Immunogenicity of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Allogeneic Hematopoietic Cell Transplant Recipients (PNEU-STEM).
BACKGROUND
Individuals who receive allogeneic hematopoietic cell transplant (allo-HCT) are immunocompromised and at high risk of pneumococcal infections, especially in the months following transplant. This study evaluated the safety and immunogenicity of V114 (VAXNEUVANCE; Merck, Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA), a 15-valent pneumococcal conjugate vaccine (PCV), when given to allo-HCT recipients.
METHODS
Participants received 3 doses of V114 or PCV13 (Prevnar 13; Wyeth LLC) in 1-month intervals starting 3-6 months after allo-HCT. Twelve months after HCT, participants received either PNEUMOVAX 23 or a fourth dose of PCV (if they experienced chronic graft vs host disease). Safety was evaluated as the proportion of participants with adverse events (AEs). Immunogenicity was evaluated by measuring serotype-specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers (GMTs) for all V114 serotypes in each vaccination group.
RESULTS
A total of 274 participants were enrolled and vaccinated in the study. The proportions of participants with AEs and serious AEs were generally comparable between intervention groups, and the majority of AEs in both groups were of short duration and mild-to-moderate intensity. For both IgG GMCs and OPA GMTs, V114 was generally comparable to PCV13 for the 13 shared serotypes, and higher for serotypes 22F and 33F at day 90.
CONCLUSIONS
V114 was well tolerated in allo-HCT recipients, with a generally comparable safety profile to PCV13. V114 induced comparable immune responses to PCV13 for the 13 shared serotypes, and was higher for V114 serotypes 22F and 33F. Study results support the use of V114 in allo-HCT recipients. Clinical Trials Registration. clinicaltrials.gov (NCT03565900) and European Union at EudraCT 2018-000066-11.
Topics: Humans; Vaccines, Conjugate; Transplant Recipients; Hematopoietic Stem Cell Transplantation; Antibodies, Bacterial; Pneumococcal Infections; Pneumococcal Vaccines; Double-Blind Method; Immunoglobulin G; Immunogenicity, Vaccine
PubMed: 37338158
DOI: 10.1093/cid/ciad349 -
Pediatric Emergency Care Dec 2023Community-acquired pneumonia (CAP) is the most common cause of childhood mortality globally. In the United States, CAP is a leading cause of pediatric hospitalization...
Community-acquired pneumonia (CAP) is the most common cause of childhood mortality globally. In the United States, CAP is a leading cause of pediatric hospitalization and antibiotic use and is associated with substantial morbidity. There has been a dramatic shift in microbiological etiologies for CAP in children over time as pneumococcal pneumonia has become less common and viral etiologies have become predominant. There is no commonly agreed on approach to the diagnosis of CAP in children. When indicated, antimicrobial treatment should consist of narrow-spectrum antibiotics. In this article, we will describe the current understanding of the microbiological etiologies, clinical presentation, diagnostic approach, risk factors, treatment, and future directions in the diagnosis and management of pediatric CAP.
Topics: Child; Humans; United States; Pneumonia; Anti-Bacterial Agents; Hospitalization; Community-Acquired Infections
PubMed: 38019716
DOI: 10.1097/PEC.0000000000003070 -
Neuroimaging Clinics of North America Feb 2024Stroke is a complication of many central nervous system (CNS) infections, but only a few present with stroke without other symptoms or signs of CNS infection. Chief... (Review)
Review
Stroke is a complication of many central nervous system (CNS) infections, but only a few present with stroke without other symptoms or signs of CNS infection. Chief among these are varicella zoster virus (VZV) and syphilis. Delayed cerebral vasculopathy after successful treatment of bacterial meningitis, most commonly pneumococcal, is an emerging entity with uncertain pathogenesis.
Topics: Humans; Herpes Zoster; Herpesvirus 3, Human; Stroke
PubMed: 37951699
DOI: 10.1016/j.nic.2023.06.001