Pneumococci isolated from children in community-based practice differ from isolates identified by population and laboratory-based invasive disease surveillance.

BACKGROUND: Characterizing strains causing noninvasive and invasive pneumococcal disease (IPD) may inform the impact of new pneumococcal conjugate vaccines (PCVs). METHODS: During 2011-2019, among children aged 6-36 months, pneumococcal serotype distribution and antibiotic non-susceptibility of nasopharyngeal and middle ear fluid (MEF) isolates collected at onset of acute otitis media (AOM) in Rochester, New York were compared with IPD isolates from Active Bacterial Core surveillance (ABCs) across 10 U.S. sites. RESULTS: From Rochester, 400 (nasopharyngeal) and 156 (MEF) pneumococcal isolates were collected from 259 children. From ABCs, 907 sterile-site isolates were collected from 896 children. Non-PCV serotypes 35B and 21 were more frequent among the Rochester AOM cases, while serotypes 3, 19A, 22F, 33F, 10A, and 12F contained in PCVs were more frequent among ABCs IPD cases. The proportion of antibiotic non-susceptible pneumococcal isolates was generally more common among IPD cases. In 2015-2019, serotype 35B emerged as the most common serotype associated with multiclass antibiotic non-susceptibility for both the Rochester AOM and ABCs IPD cases. CONCLUSIONS: Pneumococcal isolates from children in Rochester with AOM differ in serotype distribution and antibiotic susceptibility compared to IPD cases identified through U.S. surveillance. Non-PCV serotype 35B emerged as a common cause of AOM and IPD.

Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype.

OBJECTIVES: Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis. METHODS: A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response. RESULTS: Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV. CONCLUSIONS: Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis.

Invasive pneumococcal surveillance to assess the potential benefits of extended spectrum conjugate vaccines (PCV15/PCV20) in older adults.

The introduction of pneumococcal conjugate vaccines (PCV) into the childhood vaccination programme has reduced invasive pneumococcal disease (IPD). Although anticipated from data elsewhere, surveillance in Ireland has confirmed reductions in IPD amongst those ⩾65 years of age due to a decline of PCV serotypes in this age group. Currently, direct protection against IPD in the elderly is focused on immunisation with the 23-valent pneumococcal polysaccharide vaccine (PPV23). However, immunity may not be as effective as with PCV and, furthermore, PPV23 uptake is poor in Ireland. Hence, consideration should be given to providing a PCV to this age group.

[Pneumococcal meningitis in children in Iceland - case report and summary].

An eleven month old girl was referred to the pediatric emergency department at Landspitali Hospital due to fever and lethargy. On examination she was acutely ill with fluctuating level of conciousness. She deteriorated quickly after arrival at the emergency department and was diagnosed with pneumococcal meningitis. In the past year several cases of bacterial meningitis have been diagnosed with Streptococcus pneumoniae as the most common pathogen. The disease causing serotypes have been serotypes that were not in the vaccine that was used in iceland and the Icelandic health authorities have decided to change the vaccination programme accordingly.

The latest news in France before distribution of third-generation pneumococcal conjugate vaccines.

INTRODUCTION: In 2023 in France, 15 valent- pneumococcal conjugate vaccines (PCV15) have been recommended as alternatives to PCV13 for children < 2 years. PCV20 has been recommended for at-risk adults but not yet for infants, while PCV21 targets older adults. We endeavored to estimate the potential benefit of new pneumococcal vaccines in preventing invasive pneumococcal infections by comparing serotype extension to PCV13. PATIENTS AND METHODS: The National Reference Centre for Pneumococci distributed S. pneumoniae IPD serotypes from children and adults. RESULTS: In 2022, for children under 24 months, PCV15 and PCV20 ensured 10 % and 36 % more coverage against IPD than PCV13. For adults, PCV15, PCV20, and PCV21 covered up to 3 %, 26 %, and 50 % more IPD cases than PCV13. CONCLUSION: The new generation of pneumococcal vaccines could reduce the burden of invasive pneumococcal infections through serotype extension. Additional studies are needed in parallel to optimize their utilization and improve vaccine coverage in France.

A phase 3, single-arm, open-label study to evaluate the safety, tolerability, and immunogenicity of a 15-valent pneumococcal conjugate vaccine, V114, in a 3+1 regimen in healthy infants in South Korea (PNEU-PED-KOR).

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 µg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

Despite the use of pneumococcal vaccines, the burden of pneumococcal disease in children persists. V114, a 15-valent pneumococcal conjugate vaccine, was immunogenic and well-tolerated in healthy South Korean infants and toddlers.

PCV15, a pneumococcal conjugate vaccine, for the prevention of invasive pneumococcal disease in infants and children.

INTRODUCTION: Streptococcus pneumoniae is a causative agent of pneumonia and acute otitis media (AOM), as well as invasive diseases such as meningitis and bacteremia. PCV15 (V114) is a new 15-valent pneumococcal conjugate vaccine (PCV) approved for use in individuals ≥6 weeks of age for the prevention of pneumonia, AOM, and invasive pneumococcal disease. AREAS COVERED: This review summarizes the V114 Phase 3 development program leading to approval in infants and children, including pivotal studies, interchangeability and catch-up vaccination studies, and studies in at-risk populations. An integrated safety summary is presented in addition to immunogenicity and concomitant use of V114 with other routine pediatric vaccines. EXPERT OPINION: Across the development program, V114 demonstrated a safety profile that is comparable to PCV13 in infants and children. Immunogenicity of V114 is comparable to PCV13 for all shared serotypes except serotype 3, where V114 demonstrated superior immunogenicity. Higher immune responses were demonstrated for V114 serotypes 22F and 33F. Results of the ongoing study to evaluate V114 efficacy against vaccine-type pneumococcal AOM and anticipated real-world evidence studies will support assessment of vaccine effectiveness and impact, with an additional question of whether higher serotype 3 immunogenicity translates to better protection against serotype 3 pneumococcal disease.

Cost-Effectiveness Analysis of Routine Childhood Immunization with 20-Valent versus 15-Valent Pneumococcal Conjugate Vaccines in Germany.

This study aimed to evaluate the cost-effectiveness of routine childhood immunization with the 20-valent pneumococcal conjugate vaccine (PCV20) in a four-dose regimen (3 + 1 schedule) versus the 15-valent PCV (PCV15/V114) in a three-dose regimen (2 + 1) in Germany. The study utilized a decision-analytic Markov model to estimate lifetime costs and effectiveness outcomes for a single birth cohort in Germany. The model tracked the incidence of acute pneumococcal infections and long-term pneumococcal meningitis sequelae for both vaccination strategies. The vaccine effectiveness data were derived from published clinical trials and observational studies of PCV7 and PCV13. Indirect effects, such as herd protection and serotype replacement, were included in the model. The model adopted a societal perspective, including direct medical, direct non-medical, and indirect costs. Scenario and sensitivity analyses were performed. In the base case, PCV20 prevented more pneumococcal disease cases and deaths, with an expected gain of 96 quality-adjusted life years (QALYs) compared to V114. However, PCV20 was associated with a total incremental cost of EUR 48,358,424, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 503,620/QALY. Most of the scenario and sensitivity analyses estimated that the ICER for PCV20 exceeded EUR 150,000/QALY. Routine childhood immunization with PCV20 instead of V114 may not be an economically efficient use of healthcare resources in Germany.

Public health impact and cost-effectiveness of 15-valent pneumococcal conjugate vaccine use among the pediatric population of the United States.

BACKGROUND: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series. METHODS: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer. RESULTS: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained. CONCLUSIONS: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States.

Health and economic outcomes of 20-valent pneumococcal conjugate vaccine compared to 15-valent pneumococcal conjugate vaccine strategies for adults in Greece.

Objective: Higher valency pneumococcal conjugate vaccines (PCVs) are expected to improve protection against pneumococcal disease through coverage of additional serotypes. The aim of the present study was to evaluate the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to 15-valent pneumococcal conjugate vaccine (PCV15) alone or followed by 23-valent polysaccharide vaccine (PPV23) for adults in Greece. Methods: A published Markov model was adapted to simulate lifetime risk of clinical and economic outcomes from the public payer's perspective. The model population was stratified based on age and risk profile (i.e., low, moderate, or high-risk of developing pneumococcal disease). Epidemiologic parameters, serotype coverage and vaccines' effectiveness were based on published literature, while direct medical costs (prices €, 2022) were obtained from official sources. Main model outcomes were projected number of invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP) cases and attributable deaths, costs and quality-adjusted life-years (QALY) for each vaccination strategy. Sensitivity analyses were performed to ascertain the robustness of model results. Results: Over the modeled time horizon, vaccination with PCV20 compared to PCV15 alone or PCV15 followed by PPV23 prevents an additional 747 and 646 cases of IPD, 10,334 and 10,342 cases of NBP and 468 and 455 deaths respectively, resulting in incremental gain of 1,594 and 1,536 QALYs and cost savings of €11,183 and €48,858, respectively. PSA revealed that the probability of PCV20 being cost-effective at the predetermined threshold of €34,000 per QALY gained was 100% compared to either PCV15 alone or the combination of PCV15 followed by PPV23. Conclusion: PCV20 is estimated to improve public health by averting additional pneumococcal disease cases and deaths relative to PCV15 alone or followed by PPV23, and therefore translates to cost-savings for the public payer. Overall results showed that vaccination with PCV20 was estimated to be a dominant vaccination strategy (improved health outcomes with reduced costs) over PCV15 alone or followed by PPV23 for prevention of pneumococcal disease in adults in Greece.

Cost-Effectiveness Analysis of Routine Use of 15-Valent Pneumococcal Conjugate Vaccine in the US Pediatric Population.

This study evaluated the clinical and economic impact of routine pediatric vaccination with the 15-valent pneumococcal conjugate vaccine (PCV15, V114) compared with the 13-valent PCV (PCV13) from a societal perspective in the United States (US). A Markov decision-analytic model was constructed to estimate the outcomes for the entire US population over a 100-year time horizon. The model estimated the impact of V114 versus PCV13 on pneumococcal disease (PD) incidence, post meningitis sequalae, and deaths, taking herd immunity effects into account. V114 effectiveness was extrapolated from the observed PCV13 data and PCV7 clinical trials. Costs (2021$) included vaccine acquisition and administration costs, direct medical costs for PD treatment, direct non-medical costs, and indirect costs, and were discounted at 3% per year. In the base case, V114 prevented 185,711 additional invasive pneumococcal disease, 987,727 all-cause pneumonia, and 11.2 million pneumococcal acute otitis media cases, compared with PCV13. This led to expected gains of 90,026 life years and 96,056 quality-adjusted life years with a total saving of $10.8 billion. Sensitivity analysis showed consistent results over plausible values of key model inputs and assumptions. The findings suggest that V114 is a cost-saving option compared to PCV13 in the routine pediatric vaccination program.

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028).

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12-15 months of age. Diphtheria, tetanus, and pertussis-inactivated poliovirus (DTaP-IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP-IPV at 1-month post-dose 3 (PD3). On days 1-14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP-IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic.

Comparison of pneumococcal immunogenicity elicited by the PCV13 and PCV15 vaccines in adults 18 through 49 years of age.

AIM: Pneumococcal conjugate vaccines (PCV13, PCV15, PCV20) effectively target the capsular polysaccharides of the most common disease-causing Streptococcus pneumoniae serotypes. In this short communication, we analyzed healthy participants who received PCV13 and PCV15 vaccines as part of a recently concluded exploratory clinical trial and report antibody responses to the 13 shared serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) as well as functional OPA responses to serotype 3. METHODS: Sera from 87 adult participants (18 through 49 years of age) randomized to receive either PCV13 or PCV15 were collected (n = 46 or n = 41, respectively), from 17 study centers in the US. IgG concentrations of the 13 shared serotypes and serotype 3-specific OPA titers were analyzed before and 1 month after vaccination using internally validated assays. RESULTS: At 1 month after vaccination, IgG GMCs of the 13 shared serotypes in PCV13 were similar to those for PCV15. Specifically, serotype 3 OPA GMTs and 95% CIs were similar 1 month after vaccination for PCV13 (62.9 [48.9, 80.9]) and PCV15 (71.1 [50.9, 99.2]). CONCLUSION: In healthy participants who received either PCV13 or PCV15, similar serotype-specific responses were observed between all shared serotypes when a uniform validated internal assay was used. Of note, data from this study suggest that both vaccines induce similar functional antibody responses against pneumococcal serotype 3.

An indirect treatment comparison (ITC) and matching-adjusted indirect comparison (MAIC) between a 15-valent (V114) and a 20-valent (PCV20) pneumococcal conjugate vaccine among healthy infants.

OBJECTIVES: Immunogenicity between 15-valent V114 (PCV15) and 20-valent PCV20 pneumococcal conjugate vaccines in healthy infants is compared in an indirect treatment comparison and matching-adjusted indirect comparison. Hypotheses: immunogenicity of V114 is non-inferior to PCV20 for all PCV13 serotypes, and superior to PCV20 for serotype 3 based on lower bound margins. METHODS: Two phase 3 pivotal studies on 3 + 1 pediatric vaccination schedule at age 2, 4, 6, and 12-15 months compared V114 (N = 858) to PCV13 (N = 856) and PCV20 (N = 1001) to PCV13 (N = 987). Infant's age and race in V114 study were matched to those in PCV20 study. Primary endpoints were serotype-specific Immunoglobulin G (IgG) response rate difference (RRD) 30 days post-dose (PD)3; IgG geometric mean concentration (GMC) ratios 30 days PD3 and PD4. RESULTS: V114 was non-inferior (marginRRD>-10%-point; marginGMCratio >0.5) to PCV20 (p-value <0.001) for all endpoints. V114 was superior (marginRRD >0%-point; marginGMCratio >1.2) to PCV20 (p-value <0.001) for serotype 3: RRD was 34.5% (95%CI 27.9%-41.1%) PD3, and IgG GMC ratios were 2.39 (95%CI 2.12-2.68) PD3 and 2.15 (95%CI 1.90-2.41) PD4. CONCLUSION: Immune response to V114 administered in a 3 + 1 schedule in healthy infants was considered non-inferior to PCV20 for all 13 PCV13 serotypes and superior for serotype 3 PD3 and PD4. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers NCT03893448, NCT04382326.

Systematic Literature Review of the Epidemiological Characteristics of Pneumococcal Disease Caused by the Additional Serotypes Covered by the 20-Valent Pneumococcal Conjugate Vaccine.

Higher valency pneumococcal conjugate vaccines (PCV15 and PCV20) have been developed to address the disease burden of current non-vaccine serotypes. This review describes the epidemiological characteristics of serotypes beyond PCV13 (serotypes 8, 10A, 11A, 12F, 15B/C, 22F, and 33F; PCV20nonPCV13 serotypes). Peer-reviewed studies published between 1 January 2010 (the year PCV13 became available) and 18 August 2020 were systematically reviewed (PROSPERO number: CRD42021212875). Data describing serotype-specific outcomes on disease proportions, incidence, severity, and antimicrobial non-susceptibility were summarized for individual and aggregate PCV20nonPCV13 serotypes by age group and by type and duration of pediatric PCV immunization program. Of 1168 studies, 127 (11%) were included in the analysis. PCV20nonPCV13 serotypes accounted for 28% of invasive pneumococcal disease (IPD), although the most frequent serotypes differed between children (10A, 15B/C) and adults (8, 12F, 22F). In children, serotype 15B/C tended to be more frequently associated with pneumococcal meningitis and acute otitis media; in adults, serotype 8 was more frequently associated with pneumonia and serotype 12F with meningitis. Serotypes 10A and 15B/C in children and 11A and 15B/C in adults were often associated with severe IPD. Serotype 15B/C was also among the most frequently identified penicillin/macrolide non-susceptible PCV20nonPCV13 serotypes. These results could inform decision making about higher valency PCV choice and use.

Pneumococcal Serotype Evolution and Burden in European Adults in the Last Decade: A Systematic Review.

Pneumococcal disease is a major cause of morbidity/mortality worldwide, and vaccination is an important measure in its prevention. Despite European children being vaccinated with pneumococcal conjugate vaccines (PCVs), pneumococcal infections are still a major cause of morbidity/mortality in adults with risk conditions and their vaccination might be an important prevention strategy. New PCVs have been approved, but information is lacking on their potential impact in European adults. In our review, we searched PubMed, MEDLINE, and Embase for studies on the additional PCV20 serotypes (concerning incidence, prevalence, disease severity, lethality, and antimicrobial resistance) in European adults, between January 2010 and April 2022, having included 118 articles and data from 33 countries. We found that these serotypes have become more prevalent in both invasive and non-invasive pneumococcal disease (IPD and NIPD), representing a significant proportion of cases (serotypes 8, 12F, 22F) and more serious disease and/or lethality (10A, 11A, 15B, 22F), showing antimicrobial resistance (11A, 15B, 33F), and/or affecting more vulnerable individuals such as the elderly, immunocompromised patients, and those with comorbidities (8, 10A, 11A, 15B, 22F). The relevance of pneumococcal adult carriers (11A, 15B, 22F, and 8) was also identified. Altogether, our data showed an increase in the additional PCV20 serotypes' prevalence, accounting for a proportion of approximately 60% of all pneumococcal isolates in IPD in European adults since 2018/2019. Data suggest that adults, as older and/or more vulnerable patients, would benefit from vaccination with higher-coverage PCVs, and that PCV20 may address an unmet medical need.

New Pneumococcal Vaccines for Prevention of Invasive Pneumococcal Disease in Adult Patients With Inflammatory Bowel Disease.

Patients with inflammatory bowel disease (IBD) are at a high risk of developing invasive pneumococcal infection both before and after they are diagnosed. The Advisory Committee on Immunization Practices now endorses use of 2 new pneumococcal conjugate vaccines, PCV15 (Vaxneuvance) and PCV20 (Prevnar 20), for patients who have never received a pneumococcal conjugate vaccine or those with unknown vaccination history. Previous studies have shown that pneumococcal vaccination can decrease the risk of developing severe pneumococcal disease; therefore, it is important that patients with IBD receive pneumococcal vaccination. This report aims to inform clinicians who care for patients with IBD about the changes in immunization practices, as it pertains to pneumococcal vaccination and provides appropriate direction on administering vaccination series.

Two new pneumococcal vaccines (PCV15 [Vaxneuvance], PCV20 [Prevnar 20]) are now recommended for patients who have not received a pneumococcal conjugate vaccine or those with unknown vaccination history. This report summarizes changes in immunization practices and provides direction on vaccination series for patients with inflammatory bowel disease.

Matching-adjusted indirect comparison of pneumococcal vaccines V114 and PCV20.

BACKGROUND: V114 (15-valent pneumococcal conjugate vaccine [PCV15]) and a 20-valent PCV (PCV20) are approved for adults (≥18 years) in the United States. We present methodologies to indirectly compare immune responses to V114 versus PCV20. RESEARCH DESIGN AND METHODS: Indirect treatment comparison and matching-adjusted indirect comparison (MAIC) were performed to estimate opsonophagocytic activity (OPA) geometric mean titer (GMT) ratios of V114/PCV20 at 30 days post-vaccination with PCV13 as common comparator for 13 serotypes (STs) shared with a 13-valent PCV (PCV13) among pneumococcal vaccine-naïve adults aged ≥60 years. Data from three V114 studies were pooled (V114, N = 2,196; PCV13, N = 843). In the MAIC analysis, data were reweighted, matching participant age and sex in NCT03760146 (PCV20, N = 1,507; PCV13, N = 1,490). RESULTS: The lower bound of V114/PCV20 OPA GMT ratio for all PCV13 STs is greater than the prespecified  0.5 non-inferiority margin and those for five PCV13 STs (3, 6A, 6B, 18C, and 23F) are greater than the prespecified 1.2 superiority margin. V114 was associated with 77% greater OPA GMT for ST3 versus PCV20. CONCLUSION: V114 was non-inferior to PCV20 for all PCV13 STs and statistically superior for five PCV13 STs.

Invasive pneumococcal disease caused by serotypes 22F and 33F in Canada: the SAVE study 2011-2018.

A 15-valent conjugate vaccine that provides protection against Streptococcus pneumoniae serotypes 22F and 33F is in development. Here we report on the prevalence, antimicrobial susceptibility, and clonal structure of these serotypes in Canada. From 2011 to 2018, the SAVE study collected 11,044 invasive S. pneumoniae isolates. Of these, 9.3% (1024/11,044) and 3.8% (416/11,044) were 22F and 33F, respectively. Serotype 22F isolates were susceptible to most antimicrobials tested except clarithromycin, where susceptibility significantly decreased over time (2011: 80.4%, 2018: 52.9%, P < 0.0001). Only 1.6% of serotype 22F isolates were multidrug-resistant (MDR), while 96% of typed strains were clonal cluster (CC) 433. Serotype 33F isolates demonstrated low susceptibility to clarithromycin and trimethoprim/sulfamethoxazole (22.4% and 24.6%, respectively) and 4.8% MDR. Most serotype 33F isolates were CC100, CC673 and CC717. CC100 prevalence increased significantly over time (2011: 50.0%, 2018: 84.8%, P < 0.006). Continued surveillance of these serotypes is crucial to identify further changes in prevalence, antimicrobial susceptibility, and clonal spread.