Higher-valent Pneumococcal Conjugate Vaccines Research Articles

Immunogenicity of Current and Next-Generation Pneumococcal Conjugate Vaccines in Children: Current Challenges and Upcoming Opportunities.

Global use of pneumococcal conjugate vaccines (PCVs) with increasingly broader serotype coverage has helped to reduce the burden of pneumococcal disease in children and adults. In clinical studies comparing PCVs, higher-valency PCVs have met noninferiority criteria (based on immunoglobulin G geometric mean concentrations and response rates) for most shared serotypes. A numeric trend of declining immunogenicity against shared serotypes with higher-valency PCVs has also been observed; however, the clinical relevance is uncertain, warranting additional research to evaluate the effectiveness of new vaccines. Novel conjugation processes, carriers, adjuvants, and vaccine platforms are approaches that could help maintain or improve immunogenicity and subsequent vaccine effectiveness while achieving broader protection with increasing valency in pneumococcal vaccines.

Understanding healthcare providers' preferred attributes of pediatric pneumococcal conjugate vaccines in the United States.

As higher-valent pneumococcal conjugate vaccines (PCVs) become available for pediatric populations in the US, it is important to understand healthcare provider (HCP) preferences for and acceptability of PCVs. US HCPs (pediatricians, family medicine physicians and advanced practitioners) completed an online, cross-sectional survey between March and April 2023. HCPs were eligible if they recommended or prescribed vaccines to children age <24 months, spent ≥25% of their time in direct patient care, and had ≥2 y of experience in their profession. The survey included a discrete choice experiment (DCE) in which HCPs selected preferred options from different hypothetical vaccine profiles with systematic variation in the levels of five attributes. Relative attribute importance was quantified. Among 548 HCP respondents, the median age was 43.2 y, and the majority were male (57.9%) and practiced in urban areas (69.7%). DCE results showed that attributes with the greatest impact on HCP decision-making were 1) immune response for the shared serotypes covered by PCV13 (31.4%), 2) percent of invasive pneumococcal disease (IPD) covered by vaccine serotypes (21.3%), 3) acute otitis media (AOM) label indication (20.3%), 4) effectiveness against serotype 3 (17.6%), and 5) number of serotypes in the vaccine (9.5%). Among US HCPs, the most important attribute of PCVs was comparability of immune response for PCV13 shared serotypes, while the number of serotypes was least important. Findings suggest new PCVs eliciting high immune responses for serotypes that contribute substantially to IPD burden and maintaining immunogenicity against serotypes in existing PCVs are preferred by HCPs.

Higher-valency pneumococcal conjugate vaccines in older adults, taking into account indirect effects from childhood vaccination: a cost-effectiveness study for the Netherlands

BackgroundNew 15- and 20-valent pneumococcal vaccines (PCV15, PCV20) are available for both children and adults, while PCV21 for adults is in development. However, their cost-effectiveness for older adults, taking into account indirect protection and serotype replacement from a switch to PCV15 and PCV20 in childhood vaccination, remains unexamined.MethodsWe used a static model for the Netherlands to assess the cost-effectiveness of different strategies with 23-valent pneumococcal polysaccharide vaccine (PPV23), PCV15, PCV20, and PCV21 for a 65-year-old cohort from a societal perspective, over a 15-year time horizon. Childhood vaccination was varied from PCV10 to PCV13, PCV15, and PCV20. Indirect protection was assumed to reduce the incidence of vaccine serotypes in older adults by 80% (except for serotype 3, no effect), completely offset by an increase in non-vaccine serotype incidence due to serotype replacement.ResultsIndirect effects from childhood vaccination reduced the cost-effectiveness of vaccination of older adults, depending on the serotype overlap between the vaccines. With PCV10, PCV13, or PCV15 in children, PCV20 was more effective and less costly for older adults than PPV23 and PCV15. PCV20 costs approximately €10,000 per quality-adjusted life year (QALY) gained compared to no pneumococcal vaccination, which falls below the conventional Dutch €20,000/QALY gained threshold. However, with PCV20 in children, PCV20 was no longer considered cost-effective for older adults, costing €22,550/QALY gained. As indirect effects progressed over time, the cost-effectiveness of PCV20 for older adults further diminished for newly vaccinated cohorts. PPV23 was more cost-effective than PCV20 for cohorts vaccinated 3 years after the switch to PCV20 in children. PCV21 offered the most QALY gains, and its cost-effectiveness was minimally affected by indirect effects due to its coverage of 11 different serotypes compared to PCV20.ConclusionsFor long-term cost-effectiveness in the Netherlands, the pneumococcal vaccine for older adults should either include invasive serotypes not covered by childhood vaccination or become more affordable than its current pricing for individual use.

Predicted serotype-specific effectiveness of pneumococcal conjugate vaccines V114 and PCV20 against invasive pneumococcal disease in children

ABSTRACT Background Next-generation, higher-valency pneumococcal conjugate vaccines (PCVs), 15-valent PCV V114 and 20-valent PCV (PCV20), have been assessed by comparing their immune responses across serotypes shared with the 13-valent PCV (PCV13). Without efficacy or real-world vaccine effectiveness (VE) it becomes important to relate IgG titers to VE to aid in the interpretation of the immune response elicited by V114 and PCV20. Methods We estimated the protective antibody concentrations for each serotype in 7-valent PCV (PCV7) and PCV13 which were then used to predict the serotype-specific VE for each PCV7 and PCV13 non PCV7 serotype present in V114 and PCV20. Results The predicted effectiveness of V114 was comparable to PCV7 and PCV13 for 11 of the 13 shared serotypes (1, 4, 5, 6B, 7F, 9 V, 14, 18C, 19A, 19F, and 23F), with improved effectiveness against serotype 3 and decreased effectiveness against serotype 6A. PCV20 had predicted effectiveness comparable to PCV7 and PCV13 for 7 of the 13 shared serotypes (5, 6A, 7F, 9 V, 18C, 19F, and 23F), with decreased effectiveness against the remaining serotypes (1, 3, 4, 6B, 14, and 19A). Conclusions Prediction of serotype-specific VE values suggests that V114 retains greater effectiveness than PCV20 toward most serotypes present in PCV7 and PCV13.

Potential Impact of Higher-Valency Pneumococcal Conjugate Vaccines Among Adults in Different Localities in Germany.

Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regression. There was little spatial variation in IPD cases caused by PCV13 serotypes, which dropped from 60% of IPD cases in 2006 to 30% in 2018. Over half of IPD cases in 2018 were attributable to serotypes covered by new PCVs (PCV15, PCV20), which suggests they could further reduce the burden of IPD.

Is it time to reconsider how higher valency pneumococcal conjugate vaccines are evaluated?

Is it time to reconsider how higher valency pneumococcal conjugate vaccines are evaluated?

Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

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

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. 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. 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. 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.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

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.

Healthcare resource utilization and cost of pneumococcal disease in children in Germany, 2014–2019: a retrospective cohort study

BackgroundSince the introduction of higher valency pneumococcal conjugate vaccines in 2009, recent estimates on the economic burden of pediatric pneumococcal disease (PD) in Germany have been lacking. This study estimates healthcare resource utilization (HCRU) and medical cost associated with PDs in children < 16 years old in Germany from 2014–2019.MethodsA nationally representative sample from the Institute for Applied Health Research (InGef) German claims database was used, covering approximately 5% of the total German population. Episodes of pneumococcal pneumonia (PP), all-cause pneumonia (ACP), invasive pneumococcal disease (IPD), and acute otitis media (AOM) in children aged < 16 years were identified using ICD-10-GM codes. HCRU was estimated from annual rates of outpatient visits, outpatient antibiotic prescriptions and inpatient admissions, divided by person-years (PY) at-risk. Average direct medical costs per episode were estimated as the total cost of all HCRU, divided by the total number of episodes. The Mann–Kendall test was used to assess monotonic time trends from 2014–2019.Results During 2014–2019, 916,805 children aged < 16 years were followed up for a total of 3,608,716 PY. The average costs per episode for out-versus inpatient care associated with PP and ACP were €67 (95% CI 58–76) versus €2,606 (95% CI 1,338–3,873), and €63 (95% CI 62–63) versus €620 (95% CI 598–641), respectively. For IPD, the average medical cost per episode for out-versus inpatients were €30 (95% CI 19–42) versus €6,051 (95% CI 3,323–8,779), respectively. There were no significant trends in HCRU or costs for IPD or pneumonia over the study period, except for a significant reduction in ACP outpatient visits. A significant decrease in rate of outpatient visits and antibiotic prescribing for recurrent AOM was observed, in addition to an increase in rates of hospital admissions for simple AOM. This was paralleled by a significant increase in inpatient costs per episode for treating AOM overall, and simple AOM, over the study period.Conclusions The HCRU and cost per episode of pneumonia and IPD did not vary significantly from 2014–2019, but increased for AOM. The economic burden of pneumonia, IPD, and AOM remains substantial in Germany.

576. Burden of Pneumococcal Disease Due to Serotypes Covered by the 13-Valent and New Higher-Valent Pneumococcal Conjugate Vaccines in All Children and Children at Risk in the United States

Abstract Background Routine vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) in infants along with a catch-up option with PCV13/PPSV23 in children with underlying medical conditions (UMC) have considerably reduced invasive pneumococcal disease (IPD) and non-invasive pneumococcal disease (PD), including community acquired pneumonia (CAP) and acute otitis media (AOM), in the United State (US). However, a rise in IPD and non-invasive PD caused by non-PCV13 serotypes has been observed. A 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, are anticipated for children soon. The objective of the study was to estimate the annual cases, deaths, and economic burden of disease attributable to PCV13, PCV15, and PCV20 serotypes in children &amp;lt; 18 years old overall and those with UMC in the US. Methods Estimated annual cases, deaths and direct medical costs associated with PD caused by PCV13, PCV15 and PCV20 serotypes were calculated based on published incidence rates of IPD, CAP, and AOM, along with age-group specific serotype coverage, case fatality rates, and disease-related costs (Table 1). The PD burden in those with UMC were extrapolated based on incidence rate ratios of those with UMC vs. those without UMC. The results were reported for 0-17 years and were further stratified into 2 age groups: 0-4 and 5-17 years. Table 1:Source Data for the Calculation Results The estimated annual PD cases attributable to PCV13, PCV15, and PCV20 serotypes in those 0-17 years were 768,301, 1,275,187, and 1,656,716 and in those with UMC were 23,209, 43,579, 63,949 (Table 2.1), respectively. The estimated direct medical costs were $494, $833, $1,103 million in those 0-17 years, and $76, $127, and $186 million in those with UMC, respectively (Table 3.1). The total estimated IPD cases in children with UMC were 18% (PCV13), 20% (PCV15) and 23% (PCV20) of all estimated IPD cases in all children. Conclusion This study demonstrates that the clinical and economic burden associated with new serotypes included in higher valent PCVs are substantial and higher in children with UMCs. The result shows that PCV20 will offer broader PCV coverage in the prevention of PD in ages &amp;lt; 18 years overall and those specifically with UMC. Disclosures Alejandro D. Cane, MD, PhD, Pfizer: Full time employee|Pfizer: Stocks/Bonds Johnna Perdrizet, MPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Adriano Arguedas, Medical director, Pfizer: Stocks/Bonds.

Association of Pneumococcal Conjugate Vaccine Use With Hospitalized Pneumonia in Medicare Beneficiaries 65 Years or Older With and Without Medical Conditions, 2014 to 2017

The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described. To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older. This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022. Use of PCV13 vaccination 14 days or more before pneumonia hospitalization. Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE). At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use. The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

Building on a Strong Foundation to Address a New Era to Help Protect Against Pneumococcal Disease

Antoni Torres, Respiratory Intensive Care Unit, Department of Pneumology and Respiratory Allergy, Hospital Clinic of Barcelona, University of Barcelona, Spain, opened the symposium, noting that pneumococcal conjugate vaccines (PCV) have reduced pneumococcal disease through direct and indirect effects. However, the burden of pneumococcal disease remains substantial in adults, supporting the importance of further reducing vaccine-preventable disease and its impact on healthcare resource utilisation and public health. Mário Ramirez, Faculty of Medicine, University of Lisbon, Portugal, and Molecular Microbiology and Infection Laboratory, Institute of Molecular Medicine, University of Lisbon, Portugal, reviewed the changing serotype epidemiology of pneumococcal disease in Europe, and described important differences between pneumococcal polysaccharide vaccines and PCVs. He detailed the dramatic direct impact of PCVs in children in decreasing the burden of vaccine-type (VT) pneumococcal disease, as well as indirect effects in unvaccinated populations, particularly adults. Residual VT-disease and increases in non-PCV13 disease underscore the need for additional disease coverage that may be afforded by higher-valent PCVs. Charles Feldman, Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa, reviewed the considerable worldwide burden of lower respiratory tract infections (LRTI), including pneumococcal pneumonia. He noted that indirect effects in adults may be suboptimal, and herd effects may have reached their limit. Feldman described adult populations that should be prioritised for pneumococcal vaccination based on risk factors, and stressed the importance of a comprehensive approach to increase adult vaccination. Finally, Wendy Watson, Vaccines Clinical Research, Pfizer, Collegeville, USA, described the adult PCV20 clinical development programme, emphasising that it was built on the well-established PCV13 platform. In the Phase III clinical trial programme, PCV20 was well tolerated, with a safety profile similar to PCV13, regardless of prior pneumococcal vaccination history. Importantly, it was immunogenic across all ages studied and in those with chronic medical conditions. Wendy Watson concluded that PCV20 has the potential to simplify adult vaccination and help reduce the burden of adult pneumococcal disease.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States.

BackgroundManagement of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease.MethodsFrom January 2011 to February 2020, we evaluated 30-day nonduplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥18 years) in inpatient and outpatient settings. Isolates were required to have ≥1 AMR result for invasive (blood, cerebrospinal fluid/neurologic) or noninvasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time.ResultsOver the study period, 34 039 S. pneumoniae isolates were analyzed (20 749 [61%] from noninvasive sources and 13 290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥1 drug, and noninvasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < .001). Significant decreasing trends were observed for penicillin (−1.6%/year; P < .001), extended-spectrum cephalosporins (ESCs; −0.35%/year; P < .001), and ≥3 drugs (−0.5%/year; P < .001).ConclusionsDespite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

Distribution of Serotypes Causing Invasive Pneumococcal Disease in Children From High-Income Countries and the Impact of Pediatric Pneumococcal Vaccination.

The introduction and adoption of pneumococcal conjugate vaccines (PCVs) into pediatric national immunization programs (NIPs) has led to large decreases in invasive pneumococcal disease (IPD) incidence caused by vaccine serotypes. Despite these reductions, the global IPD burden in children remains significant. We collected serotype-specific IPD data from surveillance systems or hospital networks of all 30 high-income countries that met inclusion criteria. Data sources included online databases, surveillance system reports, and peer-reviewed literature. Percentage of serotyped cases covered were calculated for all countries combined and by PCV type in the pediatric NIP. We identified 8012 serotyped IPD cases in children <5 or ≤5 years old. PCV13 serotype IPD caused 37.4% of total IPD cases, including 57.1% and 25.2% for countries with PCV10 or PCV13 in the pediatric NIP, respectively, most commonly due to serotypes 3 and 19A (11.4% and 13.3%, respectively, across all countries). In PCV10 countries, PCV15 and PCV20 would cover an additional 45.1% and 55.6% of IPD beyond serotypes contained in PCV10, largely due to coverage of serotype 19A. In PCV13 countries, PCV15 and PCV20 would cover an additional 10.6% and 38.2% of IPD beyond serotypes contained in PCV13. The most common IPD serotypes covered by higher valency PCVs were 10A (5.2%), 12F (5.1%), and 22F and 33F (3.5% each). Much of the remaining IPD burden is due to serotypes included in PCV15 and PCV20. The inclusion of these next generation PCVs into existing pediatric NIPs may further reduce the incidence of childhood IPD.

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.

Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.

Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD. We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons). From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes. Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.

1180. Comparing Changes in Pneumococcal Meningitis Incidence to all Invasive Pneumococcal Disease Following Introduction of PCV10 and PCV13: The PSERENADE Project

BackgroundThe introduction of higher valency pneumococcal conjugate vaccines (PCV10 and PCV13) has reduced invasive pneumococcal disease (IPD) incidence. It is unknown whether the degree of reduction differs for pneumococcal meningitis, a small subset of pneumococcal disease but a major cause of severe childhood morbidity and mortality globally. We compared the impact of PCV10/13 on pneumococcal meningitis and all IPD by estimating the changes in incidence following the introduction of PCV10/13 among children < 5 years of age.MethodsData on confirmed positive cases for pneumococcus in cerebrospinal fluid (CSF) were obtained directly from surveillance sites. PCV10/13 impact on all-serotype pneumococcal meningitis and all IPD were estimated using site-specific incidence rate ratios (IRRs) at each post-PCV10/13 year relative to the pre-PCV period, using Bayesian multi-level, mixed effects Poisson regression. All-site weighted average IRRs were estimated using linear mixed-effects regression. Results were stratified by product (PCV10 vs. PCV13) and amount of prior PCV7 use (none; some (1-3 years or 4-5 years with < 70% uptake); or many (≥ 4 years with ≥ 70% uptake).Results40 surveillance sites (9 PCV10, 31 PCV13) in 28 countries, primarily high-income (82%) that had both CSF and IPD data were included in analyses. CSF+ accounted for 9.0% of IPD cases (IQR across sites: 6.2%-15.6%). The rate and amount of decline was generally similar between meningitis and IPD across all strata. At 5 years after PCV10/13 introduction, the IRRs across PCV7-use strata were 0.28-0.32 for pneumococcal meningitis and 0.22-0.43 for all IPD at PCV10-using sites, and 0.27-0.41 and 0.21-0.32, respectively, for PCV13-using sites. Only one site from the African meningitis belt contributed eligible data, which lacked pre-PCV data to estimate IRRs, but incidence rate of both IPD and meningitis decreased following PCV introduction. Figure 1. All-Site Weighted Average Incidence Rate Ratios, Children < 5 years * Total sites indicate the number of sites with incidence rate data included and pre/post sites indicate the number of sites with both pre− and post−PCV data to estimate site−specific IRRs for each outcome. The size of point estimates is relative to the number of sites with both pre− and post− data. ** Year 0 indicates the year of PCV10/13 introduction and year −1 indicates the last year of PCV7 use prior to PCV10/13 introduction.ConclusionNet declines in all-serotype IPD and CSF+ meningitis in children < 5 years were similar on average for both PCV10 and PCV13. Data from low-income, high-burden, and meningitis-belt regions were limited. Disclosures Maria Deloria Knoll, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)

70. Changes in Invasive Pneumococcal Disease among Adults Living with HIV Following Introduction of 13-Valent Pneumococcal Conjugate Vaccine, 2008–2018

BackgroundPeople living with HIV (PLHIV) are at increased risk of invasive pneumococcal disease (IPD). The 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for children in 2010, and for immunocompromised adults (including PLHIV) in series with 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated changes in IPD incidence in adults ≥19 years old by HIV status after PCV13 introduction and proportion of remaining IPD due to serotypes included in the 15- (PCV15) and 20-valent (PCV20) conjugate vaccines expected to be licensed in 2021. MethodsIPD cases were identified through CDC’s Active Bacterial Core surveillance (ABCs). HIV status was obtained from medical records. Isolates were serotyped by Quellung reaction, or whole-genome sequencing and grouped into PCV13-types, PPV11-types (unique to PPSV23), or non-vaccine types. We estimated IPD incidence (cases per 100,000 people) using national projections of ABCs cases as numerators and national case-based HIV surveillance (PLHIV) or US census data (non-PLHIV) as denominators. We compared IPD incidence in 2011–12 and 2017–18 to pre-PCV13 baseline (2008–09) by serotype groups. We assessed the proportion of IPD due to serotypes included in PCV15 and PCV20. ResultsOverall IPD incidence at baseline was 306.7 for PLHIV and 15.2 for non-PLHIV. From baseline to 2017–18, IPD incidence declined in PLHIV (-40.3%; 95% CI: -47.7, -32.3%) and non-PLHIV (-28.2%; 95% CI: -30.9, -25.5%). The largest reductions were in PCV13-type IPD during both periods (-44.2% for PLHIV and -42.2% for non-PLHIV in 2011–12; -72.5% for PLHIV and -62.2% for non-PLHIV in 2017–18) compared to baseline (Figures 1, 2). In 2017–2018, overall IPD and PCV13-type rates were 16.8 (95% CI: 15.1, 18.5) and 12.6 (95% CI: 9.9, 15.3) times as high in PLHIV vs non-PLHIV, respectively; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2% and 16.5% of IPD in PLHIV.IPD incidence rates among adults aged ≥19 years old by serotype group in PLHIV, 2008–2018 IPD incidence rates among adults aged ≥19 years old by serotype group in non-PLHIV, 2008–2018 ConclusionIPD rates declined significantly in both PLHIV and non-PLHIV during the study period due to reductions in PCV13-type IPD; however, IPD rates remained 17-fold higher in PLHIV compared to non-PLHIV, mainly due to non-PCV13 types. Higher-valent pneumococcal conjugate vaccines provide opportunities to reduce some of the remaining IPD burden in PLHIV.Disclosures William Schaffner, MD, VBI Vaccines (Consultant) Lee Harrison, MD, GSK, Merck, Pfizer, Sanofi Pasteur (Consultant)