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Vaccine Jan 2023Pneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs)... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED).
BACKGROUND
Pneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs) confer protection against PD caused by most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and additional serotypes 22F and 33F. This pivotal phase 3 study compared safety and immunogenicity of V114 and PCV13.
METHODS
1720 healthy infants were randomized 1:1 to receive a 4-dose regimen of V114 or PCV13 concomitantly with other routine pediatric vaccines. Safety was evaluated after each dose as proportion of participants with adverse events (AEs). Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured at 1-month post-dose 3 (PD3), pre-dose 4, and 1-month post-dose 4 (PD4). IgG response rates, geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) were compared between vaccination groups.
RESULTS
The proportion, maximum intensity, and duration of injection-site, systemic, and serious AEs were generally comparable between V114 and PCV13 groups. In comparison to PCV13, V114 met non-inferiority criteria for all 15 serotypes based on IgG response rates at PD3. V114 met non-inferiority criteria by IgG GMCs for all serotypes at PD3 and PD4, except for serotype 6A at PD3. V114-induced antibodies had bactericidal activity as assessed by OPA. Further, V114 met superiority criteria for shared serotype 3 and unique serotypes 22F and 33F compared to PCV13 by serotype-specific IgG GMCs at both PD3 and PD4. Immunogenicity of concomitantly administered routine pediatric vaccines was comparable in V114 and PCV13 groups.
CONCLUSIONS
In healthy infants, V114 displays acceptable safety and tolerability profiles and generates comparable immune responses to PCV13. V114 also met superiority criteria for serotypes 3, 22F, and 33F. These results support use of V114 for prevention of PD as part of routine infant vaccination schedules.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03893448; EudraCT: 2018-004109-21.
Topics: Humans; Infant; Child; Vaccines, Conjugate; Antibodies, Bacterial; Immunoglobulin G; Pneumococcal Infections; Streptococcus pneumoniae; Heptavalent Pneumococcal Conjugate Vaccine; Pneumococcal Vaccines; Double-Blind Method
PubMed: 36621410
DOI: 10.1016/j.vaccine.2022.12.054 -
MMWR. Morbidity and Mortality Weekly... Nov 2019Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.])...
Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Updated Recommendations of the Advisory Committee on Immunization Practices.
Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.]) and a 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). In 2014, the Advisory Committee on Immunization Practices (ACIP)* recommended routine use of PCV13 in series with PPSV23 for all adults aged ≥65 years based on demonstrated PCV13 safety and efficacy against PCV13-type pneumonia among adults aged ≥65 years (1). At that time, ACIP recognized that there would be a need to reevaluate this recommendation because it was anticipated that PCV13 use in children would continue to reduce disease burden among adults through reduced carriage and transmission of vaccine serotypes from vaccinated children (i.e., PCV13 indirect effects). On June 26, 2019, after having reviewed the evidence accrued during the preceding 3 years (https://www.cdc.gov/vaccines/acip/recs/grade/PCV13.html), ACIP voted to remove the recommendation for routine PCV13 use among adults aged ≥65 years and to recommend administration of PCV13 based on shared clinical decision-making for adults aged ≥65 years who do not have an immunocompromising condition, cerebrospinal fluid (CSF) leak, or cochlear implant, and who have not previously received PCV13. ACIP recognized that some adults aged ≥65 years are potentially at increased risk for exposure to PCV13 serotypes, such as persons residing in nursing homes or other long-term care facilities and persons residing in settings with low pediatric PCV13 uptake or traveling to settings with no pediatric PCV13 program, and might attain higher than average benefit from PCV13 vaccination. When patients and vaccine providers engage in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for a particular person, considerations might include both the person's risk for exposure to PCV13 serotypes and their risk for developing pneumococcal disease as a result of underlying medical conditions. All adults aged ≥65 years should continue to receive 1 dose of PPSV23. If the decision is made to administer PCV13, it should be given at least 1 year before PPSV23. ACIP continues to recommend PCV13 in series with PPSV23 for adults aged ≥19 years with an immunocompromising condition, CSF leak, or cochlear implant (2).
Topics: Advisory Committees; Aged; Centers for Disease Control and Prevention, U.S.; Humans; Pneumococcal Vaccines; United States
PubMed: 31751323
DOI: 10.15585/mmwr.mm6846a5 -
Vaccine Jan 2023Pneumococcal disease (PD) remains a major health concern globally. In children, pneumococcal conjugate vaccines (PCVs) provide protection against PD from most vaccine... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3, multicenter, randomized, double-blind study to evaluate the interchangeability of V114, a 15-valent pneumococcal conjugate vaccine, and PCV13 with respect to safety, tolerability, and immunogenicity in healthy infants (PNEU-DIRECTION).
BACKGROUND
Pneumococcal disease (PD) remains a major health concern globally. In children, pneumococcal conjugate vaccines (PCVs) provide protection against PD from most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and public health important serotypes 22F and 33F. This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens using a 3 + 1 dosing schedule when changing from PCV13 to V114 at doses 2, 3, or 4.
METHODS
900 healthy infants were randomized equally to 5 intervention groups. PCVs were administered in a 3-dose infant series at 2, 4, and 6 months of age followed by a toddler dose at 12-15 months along with concomitant routine vaccines. Safety was evaluated as the proportion of participants with adverse events (AEs). Immunoglobulin G (IgG) responses to the 15 serotypes in V114 were measured at 30 days post-dose 3 and 30 days post-dose 4 (PD4).
RESULTS
Frequencies of injection-site and systemic AEs were generally comparable across all intervention groups. At 30 days PD4 (primary endpoint), IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between mixed V114/PCV13 and 4-dose regimens of PCV13 or V114. In mixed regimens at 30 days PD4, a toddler dose of V114 was sufficient to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 22F, while at least one infant dose was needed in addition to the toddler dose to achieve IgG GMCs comparable to a 4-dose regimen of V114 for serotype 33F.
CONCLUSIONS
V114 was well tolerated with a generally comparable safety profile to PCV13. For 13 shared serotypes, both mixed regimens and the V114 4-dose regimen induced generally comparable antibody responses to 4-dose regimen with PCV13. Study results support interchangeability of V114 with PCV13 in infants.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT03620162; EudraCT: 2018-001151-12.
Topics: Humans; Infant; Heptavalent Pneumococcal Conjugate Vaccine; Vaccines, Conjugate; Double-Blind Method; Pneumococcal Vaccines; Antibodies, Bacterial; Pneumococcal Infections; Immunoglobulin G
PubMed: 36522265
DOI: 10.1016/j.vaccine.2022.10.072 -
Current Opinion in Infectious Diseases Apr 2016Pneumococcal diseases (invasive diseases, pneumonia, otitis media, and sinusitis) are among the most frequent preventable infectious diseases carrying a very high... (Review)
Review
PURPOSE OF REVIEW
Pneumococcal diseases (invasive diseases, pneumonia, otitis media, and sinusitis) are among the most frequent preventable infectious diseases carrying a very high morbidity and case fatality rate worldwide. Pneumococcal vaccination is a key element to reduce the global burden of the disease in children and adult population. Our aim is to discuss current knowledge of the epidemiology of pneumococcal disease and pneumococcal vaccines.
RECENT FINDINGS
After the introduction of conjugate vaccines (PCV7 and PCV13), rates of pneumococcal diseases because of vaccine serotypes have decreased considerably among children in the vaccine target and among nonvaccinated children and adults. Results of the Community-Acquired Pneumonia Immunization Trial in Adults demonstrated 45.6% efficacy of PCV13 against the first episode of pneumonia, 45% against first-episode nonbacteremic pneumococcal pneumonia, and 75% against the first episode of invasive pneumococcal diseases in adults older than 65 years. Recommendations for pneumococcal vaccination have changed recently in both the United States and Europe.
SUMMARY
The changing epidemiology of pneumococcal diseases should be closely investigated to assess the effectiveness and the usefulness of the current vaccination policies, and to identify future directions for preventing pneumococcal infections.
Topics: Europe; Humans; Pneumococcal Infections; Pneumococcal Vaccines; United States; Vaccination
PubMed: 26779776
DOI: 10.1097/QCO.0000000000000246 -
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 -
International Journal of Infectious... Jan 2021This review examines the epidemiology of pneumococcal disease, serotype prevalence, antibiotic resistance, and national vaccination recommendations in Thailand. The... (Review)
Review
This review examines the epidemiology of pneumococcal disease, serotype prevalence, antibiotic resistance, and national vaccination recommendations in Thailand. The incidence of invasive pneumococcal disease (IPD) and annualized hospitalization rates for pneumococcal bacteremia in Thailand were highest in children aged <5years and the elderly. The most prevalent serotype is serotype 6B, which is included in both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 [also known as PHiD-CV] and PCV13, respectively) registered in Thailand. Other common serotypes are 14, 18C, 19F, and 23F (included in both PCVs) and 6A and 19A (only included in PCV13). PCV10/PHiD-CV and PCV13 should cover 48.8%-74% and 73.2%-92% of isolates among children aged ≤5 years, respectively, and 40.0%-47.9% and 58.3%-60.9% of isolates among adults aged ≥65 years. Only PCV13 is licensed for adults in Thailand. Pneumococcal isolates were most commonly resistant to erythromycin, cefuroxime, and penicillin. Despite their demonstrated cost effectiveness and efficacy in reducing nasopharyngeal carriage and IPD, PCVs are not included in the Thai national immunization program. The serotype-specific IPD incidence in Thailand suggests that PCVs will reduce the disease burden in all age groups, but particularly in children and older adults.
Topics: Anti-Bacterial Agents; Cefuroxime; Cost of Illness; Cost-Benefit Analysis; Drug Resistance, Multiple, Bacterial; Erythromycin; Humans; Immunization Programs; Nasopharynx; Penicillins; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Serogroup; Streptococcus pneumoniae; Thailand
PubMed: 33130205
DOI: 10.1016/j.ijid.2020.10.048 -
Otolaryngology--head and Neck Surgery :... Oct 2023To assess the effect of the pneumococcal vaccine (PCV) toward the surgical management and complications of otitis media. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the effect of the pneumococcal vaccine (PCV) toward the surgical management and complications of otitis media.
DATA SOURCES
MEDLINE, EMBASE, PubMed, Scopus, and clinicaltrial.gov.
REVIEW METHODS
A systematic search was performed using a combination of keywords and standardized terms about PCV and surgical management or complications of otitis media. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies were screened by 3 independent reviewers. Risk of bias assessment, followed by meta-analysis in only randomized-controlled trials was conducted. Vaccine efficacy (VE) and 95% confidence interval (CI) were reported.
RESULTS
Of the 2649 abstracts reviewed, 27 studies were included in the qualitative analysis and were categorized into 6 outcomes: tympanostomy tube insertion, otitis media with effusion (OME), mastoiditis, spontaneous tympanic membrane (TM) perforation, recurrent acute otitis media (AOM), and severe AOM. Fifteen studies were included in the meta-analysis to evaluate the rate of tympanostomy tube insertion, OME, and recurrent AOM. PCV was significantly more effective in lowering the rate of tympanostomy tube insertion (VE, 22.2%; 95% CI, 14.6-29.8) and recurrent AOM (VE, 10.06%; 95% CI, 7.46-12.65) when compared with the control group, with no significant difference in reducing the incidence of OME. The qualitative analysis revealed that PCV had efficacy in preventing severe AOM and spontaneous TM perforation but the effect on mastoiditis remained unclear.
CONCLUSION
The PCV was effective in reducing the rate of tympanostomy tube insertion and the incidence of recurrent AOM with a nonsignificant effect in preventing OME in children.
Topics: Child; Humans; Infant; Pneumococcal Vaccines; Mastoiditis; Otitis Media; Otitis Media with Effusion; Middle Ear Ventilation
PubMed: 36924215
DOI: 10.1002/ohn.327 -
Scientific Reports Dec 2021In a cross-sectional study, with the use of molecular methods, we aimed to gain insight into oropharyngeal pneumococcal colonization over time in 1212 Greek children...
Molecular surveillance of pneumococcal carriage following completion of immunization with the 13-valent pneumococcal conjugate vaccine administered in a 3 + 1 schedule.
In a cross-sectional study, with the use of molecular methods, we aimed to gain insight into oropharyngeal pneumococcal colonization over time in 1212 Greek children recruited in general pediatric settings throughout the country; they were fully vaccinated with PCV13 (3 + 1 schedule). A single sample was obtained from each child at a time interval of 26 days to 70 months after administration of the 4th (booster) PCV13 dose; sampling time was divided into six time intervals. Carriage of Streptococcus pneumoniae was detected by real-time PCR targeting the lytA gene and isolates were serotyped by singleplex real-time PCR assays. Multiple control procedures to avoid false-positive results were applied. We showed an overall S. pneumoniae carriage rate of 48.6%. Serotyping identified typeable isolates in 82% of the total lytA-positive samples. Non-PCV13 serotypes represented 83.8% of total isolates when excluding serogroups with mixed PCV13 and non-PCV13 serotypes. In multivariate analysis daycare/school attendance emerged as the main contributing factor. Notably, serotypes 19A and 3 were the only two PCV13 serotypes the colonization rate of which increased over time (χ for trend P < 0.001 and P = 0.012, respectively). The application of the SP2020 gene on lytA-positive serotyped samples showed pneumococcal colonization in 97% of cases, and the overall colonization profile over time closely resembled that of the lytA gene. With the provisions of the methodological approach and age group of our study, the use of the oropharynx emerges as a reliable alternative to the nasopharynx in estimating pneumococcal carriage in epidemiological studies.
Topics: Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Immunization; Infant; Male; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34969968
DOI: 10.1038/s41598-021-03720-y -
Archives of Pharmacal Research Aug 2017Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other... (Review)
Review
Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other microorganisms. Streptococcus pneumoniae, a gram-positive bacterium with over 90 serotypes, is the most common causative agent. Moreover, comorbid factors including heart failure, renal disease, and pulmonary disease could increase the risk of pneumococcal pneumonia. Since the advent of the pneumococcal vaccine in the 1980s, the incidence of pneumonia has decreased significantly. However, current vaccines confer only limited protection against serotypes included in the vaccine. Thus, to overcome this limitation, new types of pneumococcal vaccines have been sought and under clinical trials. In this review, we discuss pneumonia and summarize the various types of pneumococcal vaccines in progress.
Topics: Animals; Humans; Incidence; Pneumococcal Vaccines; Pneumonia, Pneumococcal; Risk Factors; Streptococcus pneumoniae
PubMed: 28735461
DOI: 10.1007/s12272-017-0933-y -
Expert Review of Vaccines Mar 2020: This review analyzes the efficacy of pneumococcal vaccinations in lung transplant patients before and after transplantation.: This review addresses the risk for... (Review)
Review
: This review analyzes the efficacy of pneumococcal vaccinations in lung transplant patients before and after transplantation.: This review addresses the risk for respiratory infections, in particular pneumococcal infections, in lung transplantation patients in the context of immunodeficiency and immunosuppressive medication. Vaccination is recommended to counteract the increased risk of pneumococcal infection, and the relevant guidelines are discussed in this review. The design of specific vaccination schedules is required because of the impaired antibody response in specific patient categories.: Lung transplantation candidates should be vaccinated with pneumococcal vaccines prior to transplantation. Currently, the 23-valent pneumococcal polysaccharide vaccine offers the broadest coverage, but the antibody response should be monitored. New generation pneumococcal conjugate vaccines with equally broad serotype coverage could be used in the future. During the post-transplantation period, the immune status of the patients should be monitored regularly, and vaccination should be repeated when indicated.
Topics: Antibody Formation; Humans; Immunization Schedule; Lung Transplantation; Pneumococcal Infections; Pneumococcal Vaccines; Practice Guidelines as Topic; Vaccination
PubMed: 32133883
DOI: 10.1080/14760584.2020.1738224