Prior Pneumococcal Vaccination Research Articles

Comparative Effectiveness of Pneumococcal Vaccination Strategies to Prevent Invasive Pneumococcal Disease: A Population-Based Cohort Study at the Veterans Health Administration in the United States

ObjectivesComparative effectiveness of pneumococcal 13-valent conjugate vaccine (PCV13), 23-valent polysaccharide vaccine (PPSV23), and their combinations for adults in preventing invasive pneumococcal disease (IPD) has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing IPD, using population-based data from the Veterans Health Administration (VHA) in the United States (US). MethodsWe included all patients who were between 65 and 74 years, had established primary care within VHA between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrollment to the onset of IPD, considering death a competing risk event, and used Cox regression models to estimate cause-specific hazards. PCV13 only, PPSV23 only, PCV13 after PPSV23, and PPSV23 after PCV13 were incorporated into models as time-dependent covariates. Patient demographics and comorbidities were also included in the model. Results3,044,067 patients were enrolled in the cohort, with 863,958 deaths (28.4%) and 1,731 cases of IPD (0.06%) during the study period. The overall incidence rate of IPD in this population was 5.36 per 100,000 patient-years. 921,070 patients (30.3%) received at least one dose of effective pneumococcal vaccine. In multivariate analysis adjusted for comorbidities, PCV13 alone was not associated with the reduced risk of IPD, while PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR]: 0.70 [95% confidence interval (CI): 0.59-0.83]). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR: 0.54 [0.36-0.83]) compared to PPSV23 followed by PCV13 (aHR: 0.73 [0.58-0.91]). ConclusionsIn this large cohort study at the VHA, the combination of PCV13 and PPSV23, particularly PCV13 followed by PPSV23, was associated with a lower risk of IPD, indicating additional benefits in combined vaccinations with potential importance in vaccination order. Further studies are needed to evaluate the effect of newer pneumococcal vaccines.

A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-Experienced Adults 50 Years of Age or Older (Stride-6).

Pneumococcal diseases (PD) cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from pneumococcal serotypes responsible for the majority of residual PD. This phase 3 study evaluated safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-experienced adults ≥50 years. A total of 717 adults were enrolled to receive a single dose of pneumococcal vaccine as follows: Cohort 1 (n=350) previously received PPSV23 and were randomized 2:1 to receive V116 or PCV15, respectively; Cohort 2 (n=261) previously received PCV13 and were randomized 2:1 to receive V116 or PPSV23, respectively; Cohort 3 (n=106) previously received PPSV23+PCV13, PCV13+PPSV23, PCV15+PPSV23, or PCV15 and all received open-label V116. Immunogenicity was evaluated 30 days postvaccination using opsonophagocytic activity (OPA) geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) for all V116 serotypes. Safety was evaluated as the proportion of participants with adverse events (AEs). V116 was immunogenic across all 3 cohorts as assessed by serotype-specific OPA GMTs and IgG GMCs postvaccination for all 21 serotypes. V116 elicited comparable immune responses to serotypes shared with PCV15 (Cohort 1) or PPSV23 (Cohort 2), and higher immune responses to serotypes unique to V116. The proportions of participants with solicited AEs were generally comparable across cohorts. V116 is well tolerated with a safety profile comparable to currently licensed pneumococcal vaccines and generates IgG and functional immune responses to all V116 serotypes, regardless of prior pneumococcal vaccine received.

Protective Effects from Prior Pneumococcal Vaccination in Patients with Chronic Airway Diseases during Hospitalization for Influenza-A Territory-Wide Study.

Influenza is an important respiratory viral pathogen in adults, with secondary bacterial pneumonia being a common complication. While pneumococcal vaccines can prevent pneumococcal pneumonia and invasive pneumococcal disease, whether they can also prevent the severe in-hospital outcomes among patients hospitalized for influenza has not been examined. A territory-wide retrospective study was conducted in Hong Kong, which included all adult patients having chronic airway diseases (asthma, bronchiectasis, and chronic obstructive pulmonary disease) hospitalized for influenza and who had received seasonal influenza vaccine. The occurrence of secondary bacterial pneumonia, mortality, and other severe in-hospital outcomes were compared among subjects with or without pneumococcal vaccination. There was a total of 3066 eligible patients who were hospitalized for influenza in public hospitals in Hong Kong from 1 January 2016 to 30 June 2023. Completed pneumococcal vaccination with PSV23/PCV13 conferred protection against secondary bacterial pneumonia, all-cause mortality, and respiratory cause of mortality with adjusted odds ratios of 0.74 (95% CI = 0.57-0.95, p = 0.019), 0.12 (95% CI = 0.03-0.53, p = 0.005), and 0.04 (95% CI = 0.00-0.527, p = 0.0038), respectively.

Prior pneumococcal vaccination improves in-hospital mortality among elderly population hospitalized due to community-acquired pneumonia

BackgroundPneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients.MethodsThe data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown.ResultsA total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P < 0.001), and showed higher in-hospital improvement (97.6 vs. 95.0%; P < 0.001) and lower 30-day mortality (2.6 vs. 5.3%; P < 0.001). After adjusting confounding factors such as age, gender, CURB score and CCI score, the vaccinated group demonstrated a significant reduction in 30-day mortality (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.41–0.81; P < 0.01) and in-hospital mortality (HR 0.53, 95% CI0.37–0.78; P < 0.001) compared to the unvaccinated group in multivariate analysis. Vaccinated group showed better 30-day survival than those in non-vaccinated group (log-rank test < 0.05).ConclusionsAmong elderly hospitalized CAP patients, prior pneumococcal vaccination was associated with improved in-hospital mortality and 30-day mortality.

Effectiveness of a Program to Raise Awareness About Pneumococcal Vaccination Among Physicians and Patients with Chronic Respiratory Diseases: A Multicenter Cohort Study.

There is a need to increase patient and clinician awareness on the effectiveness of pneumococcal vaccination in at-risk groups. The aim of the study was to evaluate the effect of reminders for physicians and patients using the vaccination tracking system created in the hospital information management system (HIMS) on the vaccination rate, and the effect of pneumococcal vaccination on pneumonia-related hospitalization and mortality over a 12-month period. This prospective observational cohort study was undertaken during a 2-year period in 3 tertiary care centers. Patients were followed up for 12 months following vaccination, and hospital admissions and mortality were recorded via HIMS. During the campaign, HIMS transmitted pneumococcal immunization reminder messages in accordance with guideline recommendations to physicians' computers and patients' mobile phones. Educational posters on pneumococcal vaccination were posted in outpatient clinics. Regular seminars on the evidence for pneumococcal vaccination were organized. All patients who were hospitalized during the follow-up period for chronic obstructive pulmonary disease (COPD), asthma, lung cancer, or pneumonia were analyzed in relation to their vaccination history regarding clinical outcomes. A total of 29530 patients were included in the study. During the study period, the annual vaccination rate increased by 74.4% and reached 4.8% in 3 hospitals (P = .001). The rates were 3.9% in patients older than 65 years without comorbidities and 5.2% in those with COPD and asthma (P = .002). In pneumococcal vaccine recipients, pneumonia-related hospital mortality was lower (relative risk (RR) = 0.19, CI 0.09-0.35, P < .001). It is possible to raise the rate of pneumococcal vaccination through awareness campaigns. Individuals with COPD and asthma are more willing to receive pneumococcal vaccination. Among patients hospitalized for pneumonia, prior pneumococcal vaccination is associated with lower mortalit.

Severity of Exacerbation in Pneumococcal Vaccinated versus Unvaccinated Patients with Exacerbation of Chronic Obstructive Pulmonary Disease: A Post hoc Analysis of Presentation Status of the Subjects of HOPE Chronic Obstructive Pulmonary Disease Study

Background: Acute exacerbations occur with varying frequency and severity and impact the natural course of chronic obstructive pulmonary disease (COPD) patients. Pneumococcal vaccination has been shown to decrease the incidence of community-acquired pneumonia and exacerbation rate in COPD patients. There is a paucity of data on the influence of pneumococcal conjugate vaccination on the severity of COPD exacerbations. Objectives: The objectives of this study were to evaluate the severity of exacerbation in pneumococcal vaccinated (vaccinated with 13-valent conjugate vaccine) versus unvaccinated COPD subjects hospitalized with acute exacerbation. Materials and Methods: This was a post hoc analysis of the severity of exacerbation in the subjects of HOPE COPD study. This involved the collection of clinical, radiological, and laboratory data of 120 COPD patients who were hospitalized with an acute exacerbation, 60 of whom had prior pneumococcal vaccination and 60 were unvaccinated. Data of COPD patients at the time of presentation with acute exacerbation were analyzed. Comparison was made between severity parameters such as presence of fever, leukocytosis, respiratory failure, multilobar consolidation, hypotension needing inotropic support, and presence of sepsis between pneumococcal vaccinated and unvaccinated subjects. Results: The occurrence of multilobar consolidation was substantially less in the vaccinated group (60% vs. 6.7%; P = 0.0001). The incidence of fever, leukocytosis, and elevated C-reactive protein was significantly higher in the unvaccinated group. Need for intensive care unit care was higher in the unvaccinated group (58.3% vs. 30% with P = 0.019). The occurrence of new-onset respiratory failure was similar in both the groups although type 2 failure with respiratory acidosis was more in the unvaccinated group. Patients in the unvaccinated group had a higher incidence of sepsis and need for inotropic support as well as assisted ventilation. Conclusions: Prior immunization with 13-valent pneumococcal conjugate vaccine ameliorates the severity of exacerbation in COPD patients needing hospitalization. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalization with acute exacerbation.

1160. Comparative Effectiveness of Pneumococcal Vaccination Strategies to Prevent Invasive Pneumococcal Disease: A Cohort Study at the Veterans Health Administration

Abstract Background The direct impact of a combined vaccination strategy pneumococcal 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPSV23) for adults in preventing pneumococcal infections has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing the most severe form of pneumococcal infections, invasive pneumococcal disease (IPD), by comparing the risk of IPD stratified by the use of PCV13, PPSV23, and their combinations. Methods We included all patients who were 65 years or older, had established primary care within the Veterans Health Administration (VHA) between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrollment to the onset of culture-proven IPD, considering death a competing risk event, and constructed a Cox regression model to estimate cause-specific hazards. PCV13 only, PPSV23 only, and PCV13 + PPSV23 were incorporated into the model as a time-dependent exposure variable, and we estimated hazard ratios (HRs) associated with them. We also considered a waning effect by incorporating time-by-vaccine interaction terms in the model to estimate continuously changing time-dependent hazards. Results 5,069,917 patients were enrolled in the cohort (male: 96.5%; median age: 72 [IQR: 65-79]). 1,217,349 patients received at least one dose of pneumococcal vaccine during the study period. The overall incidence rate of IPD was 9.1 per 100,000 patient-years. In crude analysis, all pneumococcal vaccines were associated with lower HRs for IPD, and there was an additive benefit of PCV13 and PPSV23 (Tables 1 and 2). In multivariate analysis, associations between PCV13 alone and PPSV23 alone were no longer statistically significant after adjusting for age and comorbidities, but PCV13 + PPSV23 was significantly associated with lower HR for IPD. No time-by-vaccine interaction term was significant. Conclusion In this large cohort study at the VHA, neither vaccine by itself appeared to lower the risk of IPD, but the combination of PCV13 and PPSV23 was associated with a significantly lower risk. In addition, we did not observe evidence of a waning effect to prevent IPD. Further studies are needed to evaluate the effect of newer pneumococcal vaccines. Disclosures Michihiko Goto, MD MSCI, Merck &amp; Co.: Grant/Research Support

Predictors of serological non-response to the 13-valent pneumococcal conjugate vaccine followed by the 23-valent polysaccharide vaccine among adults living with HIV

BackgroundPeople living with HIV (PLWH) have higher incidence of pneumococcal disease compared to people without HIV. Immunization with pneumococcal vaccines is recommended, but serological non-response to pneumococcal vaccination is common for largely unknown reasons. MethodsPLWH on antiretroviral treatment and no prior pneumococcal vaccination received the 13-valent pneumococcal conjugate vaccine (PCV13) followed 60 days later by the 23-valent polysaccharide vaccine (PPV23). Serological response was evaluated 30 days post-PPV23 by antibodies against 12 serotypes covered by both PCV13 and PPV23. Seroprotection was defined as a ≥2-fold rise to a level above 1.3 µg/ml in geometric mean concentration (GMC) across all serotypes. Associations with non-responsiveness were evaluated by logistic regression. ResultsFifty-two virologically suppressed PLWH (median age of 50 years (IQR 44–55) and median CD4 count of 634 cells/mm3 (IQR 507–792)) were included. Forty-six percent (95 % CI 32–61, n = 24) achieved seroprotection. Serotypes 14, 18C and 19F had the highest, and serotypes 3, 4 and 6B the lowest GMCs. Pre-vaccination GMC levels less than 100 ng/ml were associated with increased odds of non-responsiveness compared to levels above 100 ng/ml (adjusted OR 8.7, 95 % CI 1.2–63.6, p = 0.0438). ConclusionLess than half of our study population achieved anti-pneumococcal seroprotective levels following PCV13 and PPV23 immunization. Low pre-vaccination GMC levels were associated with non-response. Further research is required to optimize vaccination strategies that achieve higher seroprotection in this high-risk group.

Hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated patients with exacerbation of COPD: results from the HOPE COPD Study.

Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.

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 phase III, multicenter, randomized, double-blind, active comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of catch-up vaccination regimens of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants, children, and adolescents (PNEU-PLAN)

BackgroundDespite widespread use of pneumococcal conjugate vaccines (PCVs) in children, morbidity and mortality caused by pneumococcal disease (PD) remain high. In addition, many children do not complete their PCV course on schedule. V114 is a 15-valent PCV that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes present in PCV13, the licensed 13-valent PCV. MethodsThis phase III descriptive study evaluated safety and immunogenicity of catch-up vaccination with V114 or PCV13 in healthy children 7 months–17 years of age who were either pneumococcal vaccine-naïve or previously immunized with lower valency PCVs (NCT03885934). Overall, 606 healthy children were randomized to receive V114 (n = 303) or PCV13 (n = 303) via age-appropriate catch-up vaccination schedules in three age cohorts (7–11 months, 12–23 months, or 2–17 years). ResultsSimilar proportions of children 7–11 months and 2–17 years of age reported adverse events (AEs) in the V114 and PCV13 groups. A numerically greater proportion of children 12–23 months of age reported AEs in the V114 group (79.0%) than the PCV13 group (59.4%). The proportions of children who reported serious AEs varied between different age cohorts but were generally comparable between vaccination groups. No vaccine-related serious AEs were reported, and no deaths occurred. At 30 days after the last PCV dose, serotype-specific immunoglobulin G geometric mean concentrations were comparable between vaccination groups for the 13 shared serotypes and higher in the V114 group for 22F and 33F. ConclusionsCatch-up vaccination with V114 in healthy individuals 7 months–17 years of age was generally well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of prior pneumococcal vaccination. These results support V114 catch-up vaccination in children with incomplete or no PCV immunization per the recommended schedule.

A trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in populations of adults ≥65 years of age with different prior pneumococcal vaccination

IntroductionA 20-valent pneumococcal conjugate vaccine, PCV20, was developed to expand protection against vaccine-preventable pneumococcal disease. PCV20 contains the components of the 13-valent pneumococcal conjugate vaccine, PCV13, and includes capsular polysaccharide conjugates for 7 additional serotypes. Thus, PCV20 may cover those additional serotypes in individuals previously vaccinated with PCV13 or provide benefits of immunization with a conjugate vaccine to individuals previously immunized with a pneumococcal polysaccharide vaccine. This study described the safety and immunogenicity of PCV20 in adults ≥65 years of age with prior pneumococcal vaccination. MethodsThis phase 3, multicenter, randomized, open-label study was conducted in the United States and Sweden. Adults ≥65 years of age were enrolled into 1 of 3 cohorts based on their prior pneumococcal vaccination history (23-valent pneumococcal polysaccharide vaccine [PPSV23], PCV13, or both PCV13 and PPSV23). Participants were randomized 2:1 within their cohort to receive a single dose of PCV20 or PCV13 in those with prior PPSV23 only, and PCV20 or PPSV23 in those with prior PCV13 only; all participants with prior PCV13 and PPSV23 received PCV20. Safety was assessed by prompted local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 1 month, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination. Immune responses 1 month after PCV20 were assessed. ResultsThe percentages of participants reporting local reactions, systemic events, and AEs after PCV20 administration were similar across cohorts and comparable with the PCV13 and PPSV23 control groups. SAE and NDCMC rates were low in all groups. Robust immune responses, including opsonophagocytic antibody responses, to the 20 vaccine serotypes were observed 1 month after PCV20 regardless of prior pneumococcal vaccination. ConclusionsPCV20 was well tolerated and immunogenic in adults ≥65 years of age previously vaccinated with different pneumococcal vaccine regimens.Clinicaltrials.gov NCT03835975.

570. “I don’t know”: The Typical Response When Taking Pneumococcal Immunization Histories in Kidney Transplant Candidates

BackgroundVaccine-preventable diseases account for significant morbidity and mortality in the kidney transplant (KT) patient population. AST Guidelines support review and documentation of pneumococcal vaccines in KT candidate infectious disease (ID) evaluations. The objective of this study is to determine the number of KT candidates screened for prior pneumococcal immunizations and the frequency of vaccines ordered by providers when indicated at Mayo Clinic Florida’s (MCF) Transplant Center.MethodsThis study was an institution-based retrospective analysis of all KT candidates evaluated at MCF from December 2, 2019 – January 14, 2020. Data collection was obtained by electronic health record review. Outcomes included known history and documentation rates of prior pneumococcal vaccinations (both Prevnar 13 and Pneumovax 23) by infectious disease (ID) providers, as well as pneumococcal vaccine order frequency during ID pre-transplant evaluation when indicated. Data analysis was done using simple descriptive statistics.ResultsSixty-one patients underwent KT evaluation during the study period. Among the 61 patients, 20 (32.8%) and 20 (32.8%) had a known prior history of receiving Prevnar 13 and Pneumovax 23 vaccinations, respectively. Vaccine history was unknown for Prevnar 13 and Pneumovax 23 in 39 (63.9%) patients. Vaccine status was not documented by ID providers in 2 (3.3%) patients. When appropriate, ID providers ordered Prevnar 13 and Pneumovax 23 in 38 (92.7%) and 41 (100%) patients, respectively. Orders included both electronic and written documentation to account for patients planning immunization elsewhere. Of the 38 patients advised to receive the Prevnar 13 vaccine, 17 (41.5%) patients were documented completing immunization. Pneumovax 23 order completion rates were not recorded since the study period only lasted six weeks due to closure by COVID-19.Table 1. Pneumococcal Vaccine History Documentation Rates Obtained by Patient Recall or Records Table 2. Pneumococcal Vaccine Order Rates at Pre-Kidney Transplant Consultations Table 3. Prevnar 13 Order Completion Rate by Documentation ConclusionThe data reflect a high number of patients who either do not recall or have documentation of prior pneumococcal vaccination available at time of KT ID evaluation. Providers documented history of pneumococcal vaccinations extremely well, ordering immunizations when necessary. This study highlights lack of portability of immunization histories in a given patient population and opportunity for improved care.Disclosures Claudia R. Libertin, MD, Pfizer, Inc. (Grant/Research Support, Research Grant or Support)

Impact of pneumococcal vaccine response on asthma exacerbation frequency in young children.

IntroductionChronic asthma is a heterogeneous disease, and increased eosinophils have been shown to predict increased asthma exacerbations, especially in adults. Recent recommendations suggest the need for supplemental PPV‐23 vaccination in older children with chronic asthma.MethodsTo investigate differences in preschool asthma, our case‐cohort study comprised of 127 children, mean age 47 months (32‐65), with a history of asthma exacerbations requiring more than three courses of systemic steroid bursts and more than six antibiotics courses in the previous year.ResultsAt baseline, mean antibody titer response to Streptococcus pneumoniae was decreased at 2.6 ± 2 out of 14 serotypes, despite prior complete pneumococcal conjugate vaccine (PCV) vaccinations. All children were readministered pneumococcal vaccinations with PCV‐13 booster and/or PPSV‐23. Mean postvaccination pneumococcal vaccine (PV) titer response was 16 ± 5 out of 23 serotypes. After contacting 91 parents/caretakers, 75 responded with less frequency of corticosteroids and antibiotic use for asthma exacerbations after PV. This group had baseline eosinophil counts of 211 ± 36/µL, while those without improvement were significantly higher at 371 ± 123/µL,*P < .05. There were no significant differences (P > .05) between the two groups from other baseline measures including demography or atopic status.ConclusionsThis subset of children with exacerbation‐prone asthma had poor antibody titer response to Streptococcus pneumoniae, even with prior complete PCV‐13 immunization. Identification of low antibody responses to PV serotypes may provide a targeted therapeutic approach to reduce wheezing exacerbations in a precise asthma phenotype in children.

Development and Validation of a Clinical Prediction Tool for Seasonal Influenza Vaccination in England

Timely identification of patients likely to miss seasonal influenza vaccination (SIV) could help health care practitioners tailor services and gain efficiency. To develop and validate a predictive model of SIV uptake among at-risk adults. This prognostic study constructed a prediction model for vaccine uptake by adults at increased risk of influenza-associated complications. Drawing from the Clinical Practice Research Datalink database's records of primary care data of 324 284 adults routinely collected at general practices across England from January 2011 to December 2016, logistic regression models were trained on data from patients registered from January 2012 to December 2013 and validated with out-of-sample data from patients registered from January 2015 to December 2016. Data were extracted from the database December 2018 and analyzed between September 2019 and December 2019. Covariates included sex, age, race/ethnicity, smoking status, socioeconomic status, previous pneumococcal vaccination, prior season SIV uptake, and clinical risk conditions. The main outcome was patient-level SIV uptake. Model performance was measured via misclassification rate, Brier score, sensitivity, specificity, and area under the curve. The training data sets consisted of 324 284 (aged 18 to 64 years) and 186 426 (aged 65 years or older) patients. The mean (SD) age in the training data among patients aged 18 to 64 years was 45 (13) years; 161 487 (49.8%) were women, and 102 133 (31.5%) were categorized as white. Among patients aged 65 years or older, the mean (SD) age was 77 (8) years; 96 169 (51.6%) were women, and 64 996 (34.9%) were categorized as white. The validation data sets consisted of 35 210 patients aged 18 to 64 years and 25 497 aged 65 years or older. The mean (SD) age in the validation data set among patients aged 18 to 64 years was 42 (14) years; 17 296 (49.1%) were women, and 13 346 (37.9%) were categorized as white. Among patients aged 65 years or older, the mean (SD) age was 73 (8) years; 13 135 (51.5%) were women, and 9641 (37.8) were categorized as white. Among patients aged 18 to 64 years, SIV uptake was 35.9% (95% CI, 35.7%-36.0%) and 32.6% (95% CI, 32.1%-33.1%) for the training and validation data sets, respectively. Among patients aged 65 years or older, SIV uptake was 83.1% (95% CI, 82.9%-83.2%) and 76.1% (95% CI, 75.5%-76.6%) for the training and validation data sets, respectively. Prior season SIV uptake and pneumococcal vaccination status were the best predictors of SIV uptake. Predicted SIV uptake probabilities for patients aged 18 to 64 years were reliable, but biased toward underpredicting, whereas, among patients aged 65 years or older, they were variable and biased toward overpredicting. Briefly, in out-of-sample validation among patients aged 18 to 64 years, misclassification rates were 0.163 to 0.164, Brier scores were 0.124 to 0.125, area under the receiver operating characteristic curve values ranged from 0.876 to 0.877, sensitivity ranged from 0.705 to 0.720, and specificity ranged from 0.896 to 0.902. In patients aged 65 years or older, misclassification rates were 0.120 to 0.125, Brier scores were 0.0953 to 0.0959, area under the receiver operating characteristic curve was 0.877, sensitivity ranged from 0.919 to 0.936, and specificity ranged from 0.680 to 0.753. This study suggests that data obtained from primary care records could accurately predict SIV uptake among at-risk adults. Further research is needed to assess the feasibility and efficacy of implementing this model in clinical settings.

Epidemiology, vaccine effectiveness, and risk factors for mortality for pneumococcal disease among hospitalised adults in Singapore: a case-control study

BackgroundStreptococcus pneumoniae infections can lead to severe morbidity and mortality, especially in patients with invasive pneumococcal disease (IPD). This study evaluated factors associated with pneumococcal disease, pneumococcal vaccine effectiveness, and risk factors for all-cause mortality in hospitalised adults with pneumococcal disease in Singapore.MethodsRetrospective case-control study of patients tested for pneumococcal disease with streptococcal urinary antigen testing and at least one sterile site culture, during their admission to a tertiary hospital in Singapore from 2015 to 2017. Patients were defined as cases of IPD or non-IPD, or as controls, based on laboratory results and clinical diagnoses. Multivariable models were constructed to determine factors associated with IPD/non-IPD, and risk factors for mortality from pneumococcal disease. Vaccine effectiveness against IPD/non-IPD was estimated using a variation of the test-negative design.ResultsWe identified 496 pneumococcal disease cases, of whom 92 (18.5%) had IPD. The mean age of cases was 69.1 ± 15.4 years, and 65.5% were male. Compared with controls (N = 9181), IPD patients were younger (mean age 61.5 ± 16.3 years, vs 72.2 ± 16.1 years in controls; p < 0.001) and with less co-morbidities [median Charlson’s score 1 (IQR 0–4), vs 3 (1–5) in controls; p < 0.001]. IPD patients also had the highest proportions with intensive care unit (ICU) admission (20.7%), inpatient mortality (26.1%) and longest median length of stay [9 (IQR 8–17) days]. On multivariable analysis, IPD was negatively associated with prior pneumococcal vaccination (adjusted relative risk ratio = 0.20, 95%CI 0.06–0.69; p = 0.011). Risk factors for mortality among pneumococcal disease patients were ICU admission, diagnosis of IPD, age ≥ 85 years and Charlson’s score > 3.ConclusionPatients with pneumococcal disease (especially IPD) were younger and had less co-morbidities than controls, but had higher risk of severe clinical outcomes and mortality. Pneumococcal vaccination effectiveness against IPD was estimated to be about 80%, and should be encouraged among high-risk patients.

Effect of atorvastatin on humoral immune response to 23-valent pneumococcal polysaccharide vaccination in healthy volunteers: The StatVax randomized clinical trial

BackgroundThe immunomodulatory effects of statins on vaccine response remain uncertain. Therefore, the objective of this study was to determine if atorvastatin enhances pneumococcal-specific antibody titer following 23-valent pneumococcal polysaccharide vaccination. MethodsDouble-blind, placebo-controlled, single-center randomized clinical trial entitled StatVax. Subjects were enrolled between June and July 2014 and followed up through September 2014. 33 healthy volunteers signed informed consent after volunteer sampling. 11 participants were excluded; 22 healthy volunteers without prior pneumococcal vaccination were enrolled and completed the study. Participants were randomized to receive a 28-day course of 40 mg atorvastatin (n = 12) or matching lactose placebo (n = 10). On day 7 of treatment, Pneumovax 23 was administered intramuscularly. The primary outcome was fold change in total pneumococcal-specific antibody titer determined by a ratio of post-vaccination titer over baseline titer. Secondary outcomes included serotype-specific pneumococcal antibody titer, seroconversion, complete blood counts (CBC), erythrocyte sedimentation rate (ESR), and serum cytokine analysis. ResultsOf the 22 randomized patients (mean age, 23.86; SD, 4.121; 11 women [50%]), 22 completed the trial. Total anti-pneumococcal antibody titer in the atorvastatin group went from a baseline mean of 32.58 (SD, 15.96) to 147.7 (SD, 71.52) μg/mL at 21 days post-vaccination while titer in the placebo group went from a mean of 30.81 (SD, 13.04) to 104.4 (SD, 45) μg/mL. When comparing fold change between treatment groups, there was a significant increase in fold change of total anti-pneumococcal antibody titer in the atorvastatin group compared to the placebo group (2-way ANOVA, p = .0177). ConclusionsAtorvastatin enhances antigen-specific primary humoral immune response to a T cell-independent pneumonia vaccination. Pending confirmation by larger cohort studies of target populations, peri-vaccination conventional doses of statins can become a novel adjuvant for poorly-immunogenic polysaccharide-based vaccines.Trial Registration: clinicaltrials.gov Identifier: NCT02097589

Influenzae and pneumococcal vaccination rate in an internal medicine ward

Vaccination against influenza virus and Streptococcus pneumoniae is a global health priority and authorities, on the basis of recent publications, have recently updated French recommendations. The aim of this study was to describe the influenzae and pneumococcal vaccination's rate in an internal medicine ward. All patients consecutively hospitalized during a 10 week-period in an internal medicine ward were included. The reasons for non-vaccination and the impact of an educational program for corrective measures were reported. Overall, 198 consecutive patients were included; 93 (47%) were immunocompromised; 142 (71.2%) had an indication for pneumococcal vaccination and 171 (86.4%) for influenza vaccination but only 16.2% and 55% of them were vaccinated against these microorganisms, respectively. Prior pneumococcal vaccination was more frequently observed in immunocompromised patients than in non-immunocompromised patients (21.1 versus 6.4%; P=0.029), but no significant difference was observed for influenza vaccine. Corrective measures were initiated in 46 patients (39%), non-immunized against S. pneumoniae. These results underline the very low prevalence of pneumococcal vaccination rate in at-risk hospitalized patients, as compared with influenza, despite recent recommendations.

Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

Trial designIn an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3–5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination.MethodsCirculating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3–5 years of age for a subgroup of study children.ResultsSerotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3–5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3–5 years of age between the three groups.ConclusionsImmunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness.Trial registrationClinicaltrials.gov NCT01414504 and NCT00219401.

Serious pneumococcal disease outbreak in men exposed to metal fume – detection, response and future prevention through pneumococcal vaccination

Welders and those exposed to metal fume are known to be at increased risk of pneumococcal pneumonia and invasive pneumococcal disease. Current UK guidance recommends that vaccination against pneumococcus be considered in those at risk of frequent or continuous occupational exposure to metal fume, taking into account the exposure control measures in place. We report an outbreak of serious pneumococcal disease that occurred between April and June 2015 among a multinational workforce exposed to metal fumes while working on the refurbishment of an oil rig in a Belfast shipyard. Four confirmed and five probable cases were identified, which occurred despite the use of environmental control measures and the availability of respiratory protective equipment. To provide direct protection to those at risk of pneumococcal disease and to eradicate carriage of pneumococcus and interrupt transmission, pneumococcal polysaccharide vaccine (PPV23) and antibiotic prophylaxis were offered to 680 individuals identified as potentially exposed to metal fume. Low levels of prior pneumococcal vaccination were reported among this target group (<1%). Genomic sequencing indicated a common strain of serotype 4 pneumococcus in two of the confirmed cases and a distinct serotype 4 in one case. The fourth confirmed case was identified as likely serotype 3 using a serotype-specific immunoassay on a urine specimen. Both serotypes 3 and 4 are vaccine-preventable strains covered by the conjugate and polysaccharide pneumococcal vaccines currently available. We propose that consideration should be given to strengthening implementation around pneumococcal vaccination for those exposed to metal fume through their work, even when other control measures are in place, to reduce the risk of future cases and outbreaks of serious pneumococcal disease.