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The Medical Letter on Drugs and... Oct 2012
Review
Topics: Adult; Age Factors; Animals; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Vaccines, Conjugate
PubMed: 23114739
DOI: No ID Found -
Epidemiology and Infection Apr 2018Because of a lack of gold standard diagnostics, a combination of multiple diagnostic tests, or composite diagnostic standard, has been used to measure pneumococcal... (Review)
Review
Because of a lack of gold standard diagnostics, a combination of multiple diagnostic tests, or composite diagnostic standard, has been used to measure pneumococcal pneumonia (PP) in pneumococcal vaccine trials. We estimated the accuracy of composite diagnostic standards for PP used in previous randomised controlled trials by simple formulas. A systematic literature review identified five eligible trials and all trials had used different combinations of diagnostic tests for PP. The estimated values of sensitivity and minimum specificity of composite diagnostic standards varied substantially between trials: 48.4% to 98.1% and 71.0% to 97.3%, respectively. Without standardizing the outcome measurements, pneumococcal vaccine efficacy estimates against PP are not comparable between trials and their pooled estimates are biased.
Topics: Diagnostic Tests, Routine; Humans; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Randomized Controlled Trials as Topic; Sensitivity and Specificity
PubMed: 29606164
DOI: 10.1017/S0950268818000651 -
Frontiers in Immunology 2019Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To...
Current guidelines encourage administering pneumococcal vaccine Prevnar-13 to patients with lupus, but whether such vaccinations affect disease severity is unclear. To address this issue, we treated 3-month-old MRL- mice, that spontaneously develop a lupus-like syndrome, with Prevnar-13 or vehicle control. After 3 months, we quantified circulating anti-Pneumococcal polysaccharide capsule (PPS) antibodies and signs of disease severity, including albuminuria, renal histology and skin severity score. We also compared immunophenotypes and function of T and B cells from treated and untreated animals. Prevnar-13 elicited the formation of anti-pneumococcal IgM and IgG. Prevnar-13 treated animals showed reduced albuminuria, renal histological lesions, and milder dermatitis compared to vehicle-treated controls. Mitigated disease severity was associated with reduced and increased T follicular helper cells (T) and T follicular regulatory cells (T), respectively, in Prevnar-treated animals. T cells from Prevnar-13 vaccinated mice showed differential cytokine production after aCD3/aCD28 stimulation, with significantly decreased IL-17 and IL-4, and increased IL-10 production compared to non-vaccinated mice. In conclusion, pneumococcal vaccination elicits anti-pneumococcal antibody response and ameliorates disease severity in MRL- mice, which associates with fewer T and increased T. Together, the data support use of Prevnar vaccination in individuals with SLE.
Topics: Animals; Antibodies, Bacterial; Disease Models, Animal; Lupus Erythematosus, Systemic; Mice; Mice, Inbred MRL lpr; Pneumococcal Vaccines; T-Lymphocytes
PubMed: 31824490
DOI: 10.3389/fimmu.2019.02695 -
Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression.Microbiology Spectrum Jun 2022Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a...
Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the >100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S. pneumoniae. All S. pneumoniae strains encode the SpnIII Restriction-Modification system. This system contains a phase-variable methyltransferase that switches specificity, and controls expression of multiple genes-a phasevarion. We examined the role of this phasevarion during pneumococcal pathobiology, and determined if phase variation resulted in differences in expression of currently investigated conserved protein antigens. Using locked strains that express a single methyltransferase specificity, we found differences in clinically relevant traits, including survival in blood, and adherence to and invasion of human cells. We also observed differences in expression of numerous proteinaceous vaccine candidates, which complicates selection of antigens for inclusion in a universal protein-based pneumococcal vaccine. This study will inform vaccine design against S. pneumoniae by ensuring only stably expressed candidates are included in a rationally designed vaccine. S. pneumoniae is the world's foremost bacterial pathogen. S. pneumoniae encodes a phasevarion (phase-variable regulon), that results in differential expression of multiple genes. Previous work demonstrated that the pneumococcal SpnIII phasevarion switches between six different expression states, generating six unique phenotypic variants in a pneumococcal population. Here, we show that this phasevarion generates multiple phenotypic differences relevant to pathobiology. Importantly, expression of conserved protein antigens varies with phasevarion switching. As capsule expression, a major pneumococcal virulence factor, is also controlled by the phasevarion, our work will inform the selection of the best candidates to include in a rationally designed, universal pneumococcal vaccine.
Topics: Humans; Methyltransferases; Phase Variation; Pneumococcal Vaccines; Streptococcus pneumoniae; Virulence
PubMed: 35536022
DOI: 10.1128/spectrum.00916-22 -
Journal of Immunology Research 2015Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal... (Review)
Review
Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies.
Topics: Age Factors; Carrier State; Child; Child, Preschool; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Incidence; Nasopharynx; Otitis Media; Outcome Assessment, Health Care; Pneumococcal Infections; Pneumococcal Vaccines; Pneumonia; Vaccination; Vaccines, Conjugate
PubMed: 26351648
DOI: 10.1155/2015/591580 -
Drugs Oct 2010The pneumococcal polysaccharide conjugate vaccine Prevenar 13® (PCV13) comprises 13 capsular Streptococcus pneumoniae polysaccharide serotypes that are individually... (Comparative Study)
Comparative Study Review
The pneumococcal polysaccharide conjugate vaccine Prevenar 13® (PCV13) comprises 13 capsular Streptococcus pneumoniae polysaccharide serotypes that are individually conjugated to nontoxic diphtheria protein (cross-reactive material [CRM(197)]). In randomized, comparator-controlled, phase III trials in healthy infants aged 2-6 months, PCV13 elicited a strong immune response against all 13 pneumococcal serotypes in terms of the proportion of vaccinees achieving reference antibody levels with a two- or three-dose primary vaccination series. Immune responses for the seven serotypes common to PCV13 and the 7-valent pneumococcal conjugate vaccine Prevenar® (PCV7) were generally similar. Antibodies to all vaccine serotypes were functional. A booster dose of PCV13 administered between 11 and 15 months of age generally boosted the immune response against all 13 serotypes, regardless of whether infants had previously received PCV13 or PCV7 during the primary vaccination phase. Robust immune responses against all serotypes were achieved when PCV13 was administered as catch-up vaccination schedules in older infants and young children aged 7-72 months. Importantly, PCV13 did not interfere with the immune responses to coadministered routine paediatric vaccines. Based on data for PCV7, it is expected that PCV13 will also display protective efficacy against invasive pneumococcal disease, otitis media and pneumonia. PCV13 was generally well tolerated, with an adverse event profile similar to that of PCV7 after any vaccine dose.
Topics: Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 20883054
DOI: 10.2165/11205110-000000000-00000 -
Clinical Microbiology and Infection :... Oct 2002Pneumococcal disease is now the leading cause of vaccine-preventable bacterial disease in children worldwide. Although a pneumococcal polysaccharide vaccine has been... (Review)
Review
Pneumococcal disease is now the leading cause of vaccine-preventable bacterial disease in children worldwide. Although a pneumococcal polysaccharide vaccine has been available for over three decades, its use has been limited due to poor immunogenicity in the most vulnerable children, aged less than 2 years. The prevalence of pneumococcal disease worldwide and the alarming global escalation of multiresistant strains of Streptococcus pneumoniae (pneumococcus) during the past decade have provided the impetus for the development and application of a new pneumococcal vaccine. The outstanding success of Haemophilus influenzae type b (Hib) conjugate vaccine in the control of invasive Hib disease is a reason to be optimistic that the pneumococcal conjugate vaccines will achieve similar results for the control of invasive pneumococcal disease. Remarkable efficacy against invasive pneumococcal disease with a seven-valent pneumococcal conjugate vaccine was demonstrated in infants and toddlers in the USA, and in February 2000 the first pneumococcal conjugate vaccine was licensed. Licensure and widespread use is likely to follow in other countries in which there is a need and the means to afford this live-saving vaccine. Active disease surveillance must be sustained globally, while active research, development of other multivalent conjugate formulations and the search for new candidate protein-based vaccines are in progress.
Topics: Adolescent; Adult; Child; Child, Preschool; Drug Resistance, Bacterial; Humans; Middle Aged; Nasopharyngeal Diseases; Pneumococcal Infections; Pneumococcal Vaccines; Polysaccharides, Bacterial; Streptococcus pneumoniae; Treatment Outcome; Vaccines, Conjugate
PubMed: 12390280
DOI: 10.1046/j.1469-0691.2002.00424.x -
Paediatric Drugs 2002PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to... (Review)
Review
UNLABELLED
PNCRM7 (Prevnar) is a pneumococcal vaccine containing seven capsular polysaccharide antigens from the bacterium Streptococcus pneumoniae, each of which is conjugated to diphtheria protein [cross-reactive material (CRM(197))]. CRM(197) is an inert but immunogenic variant of diphtheria toxoid that is also used as a carrier molecule in one Haemophilus influenzae type b conjugate vaccine. Unlike the 23-valent unconjugated pneumococcal vaccines, PNCRM7 elicits a T cell-dependent response and thus protects young children against pneumococcal disease. The immunogenicity of PNCRM7 has been demonstrated in both healthy children aged <2 years and older children in high-risk groups. Two randomized, double-blind trials conducted in the US demonstrated that all PNCRM7 serotypes were immunogenic in healthy infants and young children when compared with a control vaccine. A booster dose of PNCRM7 elicited an anamnestic response to all seven serotypes. Data from a large, randomized, double-blind study conducted in California (US) have confirmed the protective efficacy of PNCRM7 against invasive pneumococcal disease (e.g. bacteremia, meningitis) caused by serotypes included in the vaccine. The vaccine efficacy in the per-protocol analysis was 97.4% and its efficacy against invasive disease caused by any pneumococcal serotype in the intent-to-treat (ITT) analysis was 89.1%. Indeed, a postlicense surveillance study (n = 211,565) showed that the introduction and routine use of PNCRM7 was associated with a marked reduction in invasive pneumococcal disease in children <5 years of age. In addition, the US trial and another randomized, double-blind trial conducted in Finland, showed that PNCRM7 vaccine efficacy against all otitis media episodes was between 6 and 7%. PNCRM7 vaccine was generally well tolerated and had a similar local and systemic adverse events profile to other pediatric vaccines. The most common local adverse event associated with PNCRM7 administration was inflammation at the injection site, and the most common systemic adverse effect was febrile illness (> or =38 degrees C) that usually resolved without treatment. The limited available pharmacoeconomic data suggest that PNCRM7 could be cost effective depending, in part, on the manufacturer's list price of the vaccine. Results of the base case analysis in a US study showed a cost-effectiveness ratio for PNCRM7 of US dollars 80,000 per life-year saved from a societal perspective compared with US dollars 176,000 from a healthcare payer perspective, assuming a nondiscounted list price of US dollars 58 per dose (1997 costs). Concomitant administration of PNCRM7 vaccine with hepatitis B, oral polio, meningococcal oligosaccharide protein conjugate or H. influenzae type b vaccines did not affect the immunogenicity of these pediatric vaccines to a clinically relevant extent.
CONCLUSION
PNCRM7 vaccine will be of great benefit to those societies that have active immunization programs implemented. In infants and vulnerable children throughout the world, PNCRM7 vaccine has the potential to reduce the mortality and morbidity rates associated with S. pneumoniae infections. In developed countries, the vaccine will be of particular benefit in preventing disabling infections but its impact in developing countries will be more pronounced with the potential to greatly reduce mortality.
Topics: Child; Clinical Trials as Topic; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Meningococcal Vaccines; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 12175274
DOI: 10.2165/00128072-200204090-00005 -
Vaccine May 2002Pneumococcal polysaccharide vaccine is recommended in western countries for individuals at high risk of pneumococcal illness. We undertook a systematic review of... (Review)
Review
UNLABELLED
Pneumococcal polysaccharide vaccine is recommended in western countries for individuals at high risk of pneumococcal illness. We undertook a systematic review of randomised controlled trials of pneumococcal vaccine in adults, to determine the effects on clinical outcomes.
RESULTS
In industrialised populations, no benefit was detected for outcomes other than pneumococcal bacteraemia, and this did not reach statistical significance. In non-industrial populations, clear benefit was demonstrated for mortality and all-cause pneumonia.
CONCLUSION
Benefit from pneumococcal vaccination depends on the baseline risk of infection and characteristics of a given population. Evidence from randomised trials for widespread adult vaccination in industrial countries is lacking.
Topics: Adult; Humans; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 12009269
DOI: 10.1016/s0264-410x(02)00112-3 -
Current Opinion in Pulmonary Medicine Jul 2010The aim of this review is to highlight recent reports (2009) concerning empyema and the heptavalent pneumococcal conjugate vaccine. (Review)
Review
PURPOSE OF REVIEW
The aim of this review is to highlight recent reports (2009) concerning empyema and the heptavalent pneumococcal conjugate vaccine.
RECENT FINDINGS
Streptococcus pneumoniae remains the most common cause of complicated pneumonia worldwide. Moreover, the incidence of empyema is increasing in many parts of the world and nonvaccine pneumococcal serotypes have been related with this increase. The introduction of heptavalent pneumococcal conjugate vaccine has been associated with the replacement phenomenon in the nasopharynx. Replacement implies that nonvaccine serotypes acquire an ecological advantage for colonizing the nasopharynx and, consequently, increase the carriage status and, in a second step, the disease. Pneumonia with or without empyema has been the main clinical presentation related with the emergence of nonvaccine serotypes. The replacement phenomenon could be multifactorial because other factors apart from heptavalent pneumococcal conjugate vaccine can also contribute to this event.
SUMMARY
A new generation of conjugate vaccines that include new serotypes and a wider spectrum of coverage, and the protein-based vaccines that may prevent invasion and preserve colonization, should help us to achieve a positive long-term impact of pneumococcal vaccination.
Topics: Carrier State; Empyema; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 20531084
DOI: 10.1097/MCP.0b013e328338c19f