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Microbiology Spectrum Nov 2019is a Gram-Positive pathogen that is a major causative agent of pneumonia, otitis media, sepsis and meningitis across the world. The World Health Organization estimates... (Review)
Review
is a Gram-Positive pathogen that is a major causative agent of pneumonia, otitis media, sepsis and meningitis across the world. The World Health Organization estimates that globally over 500,000 children are killed each year by this pathogen. Vaccines offer the best protection against infections. The current polysaccharide conjugate vaccines have been very effective in reducing rates of invasive pneumococcal disease caused by vaccine type strains. However, the effectiveness of these vaccines have been somewhat diminished by the increasing numbers of cases of invasive disease caused by non-vaccine type strains, a phenomenon known as serotype replacement. Since, there are currently at least 98 known serotypes of , it may become cumbersome and expensive to add many additional serotypes to the current 13-valent vaccine, to circumvent the effect of serotype replacement. Hence, alternative serotype independent strategies, such as vaccination with highly cross-reactive pneumococcal protein antigens, should continue to be investigated to address this problem. This chapter provides a comprehensive discussion of pneumococcal vaccines past and present, protein antigens that are currently under investigation as vaccine candidates, and other alternatives, such as the pneumococcal whole cell vaccine, that may be successful in reducing current rates of disease caused by .
Topics: Animals; Bacterial Proteins; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae
PubMed: 31858954
DOI: 10.1128/microbiolspec.GPP3-0028-2018 -
Glycoconjugate Journal Apr 2023Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use... (Review)
Review
Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use of polysaccharide-protein conjugate vaccines has been pivotal in reducing the incidence of invasive pneumococcal disease despite the emergence of non-vaccine serotypes. Notwithstanding its undoubtable success, some weaknesses have called for continuous improvement of pneumococcal vaccination. For instance, despite their inclusion in pneumococcal conjugate vaccines, there are challenges associated with some serotypes. In particular, Streptococcus pneumoniae type 3 remains a major cause of invasive pneumococcal disease in several countries.Here a deep revision of the strengths and weaknesses of the licensed pneumococcal conjugate vaccines and other vaccine candidates currently in clinical development is reported.
Topics: Humans; Pneumococcal Vaccines; Streptococcus pneumoniae; Pneumococcal Infections; Vaccination; Vaccines, Conjugate; Antibodies, Bacterial
PubMed: 36652051
DOI: 10.1007/s10719-023-10100-3 -
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 -
Acta Clinica Belgica Feb 2023Currently existing pneumococcal vaccines have contributed to a major reduction in pneumococcal disease. However, there remains an unmet need for vaccine coverage of... (Review)
Review
OBJECTIVES
Currently existing pneumococcal vaccines have contributed to a major reduction in pneumococcal disease. However, there remains an unmet need for vaccine coverage of serotypes not included in PCV13 to further reduce the burden of disease. The objective of this review is to assess the potential impact of implementation of the investigational 20-valent pneumococcal conjugate vaccine (PCV20) in the childhood and adult immunization programme in Belgium and Europe.
METHODS
A literature search was conducted to identify publications and surveillance reports concerning the effectiveness and safety of pneumococcal vaccines, epidemiological data on pneumococcal disease or serotype distribution dynamics after introduction of systematic vaccination.
RESULTS
Serotypes included in PCV20 currently account for the majority of pneumococcal disease in Belgium and Europe. In Belgium, PCV20-serotypes accounted for 71.4% of invasive pneumococcal disease (IPD) cases across all age groups in 2019, of which 39.2% were caused by PCV20-non-PCV13-serotypes. In Europe, these seven serotypes accounted for 37,6% of IPD cases in 2018. PCV20 has proven to be well tolerated in vaccine-naïve adults and elicits a substantial immune response against all serotypes included.
CONCLUSION
Due to serotype replacement following the introduction of PCV7 and PCV13, a considerable proportion of pneumococcal disease is currently caused by PCV20-serotypes. PCV20 has the potential of preventing more pneumococcal disease in children and the adult population at risk than the existing conjugate vaccines. The available evidence on safety and immunogenicity of PCV20 is promising, but further research is needed to provide data about vaccine effectiveness, immune response duration and replacement phenomenon after introduction of PCV20.
Topics: Child; Adult; Humans; Infant; Streptococcus pneumoniae; Heptavalent Pneumococcal Conjugate Vaccine; Vaccines, Conjugate; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 35171752
DOI: 10.1080/17843286.2022.2039865 -
Drugs Jun 2022The introduction of multi-valent pneumococcal vaccines around the world, such as the 13-valent pneumococcal conjugate vaccine (PCV13), has had a significant effect in... (Review)
Review
The introduction of multi-valent pneumococcal vaccines around the world, such as the 13-valent pneumococcal conjugate vaccine (PCV13), has had a significant effect in reducing the burden of disease caused by Streptococcus pneumoniae infection globally. However, S. pneumoniae serotypes not covered by PCV13 still cause significant disease. A 20-valent pneumococcal conjugate vaccine (PCV20; Prevnar20; Apexxnar) has recently been licensed for active immunisation for the prevention of invasive disease and pneumonia caused by S. pneumoniae in adults. PCV20 contains all components of PCV13 with the addition of polysaccharide conjugates of seven more serotypes, selected based on their generalised geographic distribution and relative prevalence as a cause of pneumococcal disease. The immunogenicity of PCV20 in adults has been demonstrated in a well-designed program of clinical trials which showed that PCV20 administered as a single dose by intramuscular injection induced robust immune responses to all 20 S. pneumoniae serotypes covered by the vaccine. PCV20 was well tolerated, with a tolerability and safety profile similar to that for PCV13. By expanding the coverage of disease-causing S. pneumoniae serotypes relative to other PCVs, PCV20 presents a valuable new tool with the potential to further reduce the impact of pneumococcal disease.
Topics: Adult; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 35793027
DOI: 10.1007/s40265-022-01733-z -
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... Jan 2022In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme...
Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2022.
In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework, using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations.
Topics: Adult; Advisory Committees; Aged; Centers for Disease Control and Prevention, U.S.; GRADE Approach; Health Planning Guidelines; Humans; Middle Aged; Pneumococcal Vaccines; United States; Vaccines, Conjugate
PubMed: 35085226
DOI: 10.15585/mmwr.mm7104a1 -
The Pediatric Infectious Disease Journal Oct 2021The development and widespread use of pneumococcal conjugate vaccines (PCVs) substantially reduced the global burden of pneumococcal disease. Expanding the serotypes... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The development and widespread use of pneumococcal conjugate vaccines (PCVs) substantially reduced the global burden of pneumococcal disease. Expanding the serotypes covered by PCVs may further reduce disease burden. A 20-valent PCV (PCV20) has been developed to add coverage for 7 additional serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F) to those in the existing 13-valent PCV (PCV13). This phase 2 study evaluated the safety, tolerability and immunogenicity of PCV20 in healthy US infants.
METHODS
In this randomized, active-controlled, double-blind study, 460 infants were randomized 1:1 to receive a 4-dose series of either PCV20 or PCV13 at 2, 4, 6 and 12 months of age. Solicited local reactions and systemic events, adverse events (AEs) and serious AEs were recorded. Immunogenicity was assessed by measuring serotype-specific IgG concentrations and opsonophagocytic activity titers at 1 month after Dose 3, before Dose 4 and 1 month after Dose 4.
RESULTS
Of 460 infants, 82.8% completed the 1-month visit after Dose 4. Local reactions and systemic events were mostly mild to moderate in severity and similar between the PCV20 and PCV13 groups. Treatment-related AEs were uncommon, with no related serious AEs or deaths reported. IgG and opsonophagocytic activity responses elicited by PCV20 were robust and demonstrated a booster response after Dose 4.
CONCLUSIONS
Administration of PCV20 in US infants was well tolerated, with a safety profile similar to PCV13, and induced robust serotype-specific immune responses. These findings support continued development of PCV20 in the pediatric population.
Topics: Antibodies, Bacterial; Double-Blind Method; Female; Humans; Immunogenicity, Vaccine; Immunoglobulin G; Infant; Male; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; United States; Vaccines, Conjugate
PubMed: 34525007
DOI: 10.1097/INF.0000000000003277 -
Vaccine Jun 2022Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in... (Observational Study)
Observational Study
BACKGROUND
Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).
METHODS
We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose.
RESULTS
The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively.
CONCLUSIONS
PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.
Topics: Child; Humans; Immunization Schedule; Infant; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 35637067
DOI: 10.1016/j.vaccine.2022.05.011 -
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