23-valent Polysaccharide Vaccine 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 13-valent pneumococcal 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. 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 enrolment 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. ResultsA total of 3 044 067 patients were enrolled in the cohort, with 863 958 deaths (28.4%) and 1731 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. A total of 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, whereas PPSV23 had protective association with IPD incidence (adjusted hazard ratio [aHR], 0.70; 95% CI, 0.59–0.83). When combined, PCV13 followed by PPSV23 had a stronger protective association (aHR, 0.54; [0.36–0.83]) compared with PPSV23 followed by PCV13 (aHR, 0.73; [0.58–0.91]). Discussion: In 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.

Pneumococcal Vaccination Strategies in 50-Year-Olds to Decrease Racial Disparities: A US Societal Perspective Cost-Effectiveness Analysis

ObjectivesThis study assesses the impact of expanding pneumococcal vaccination to all 50-year-olds to decrease racial disparities by estimating from the societal perspective, the cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) and 15-valent conjugate vaccine followed by 23-valent polysaccharide vaccine (PCV15/PPSV23) for 50-year-olds. MethodsA Markov model compared the cost-effectiveness of PCV20 or PCV15/PPSV23 in all general population 50- and 65-years-olds compared with current US recommendations and with no vaccination in US Black and non-Black cohorts. US data informed model parameters. Pneumococcal disease societal costs were estimated using direct and indirect costs of acute illness and of pneumococcal-related long-term disability and mortality. Hypothetical 50-year-old cohorts were followed over their lifetimes with costs and effectiveness discounted 3% per year. Deterministic and probabilistic sensitivity analyses assessed model uncertainty. ResultsIn Black cohorts, PCV20 for all at ages 50 and 65 was the least costly strategy and had greater effectiveness than no vaccination and current recommendation strategies, whereas PCV15/PPSV23 at 50 and 65 cost more than $1 million per quality-adjusted life year (QALY) gained compared with PCV20 at 50 and 65. In non-Black cohorts, PCV20 at 50 and 65 cost $62 083/QALY and PCV15/PPSV23 at 50 and 65 cost more than $1 million/QALY with current recommendations, again being more costly and less effective. In probabilistic sensitivity analyses, PCV20 at 50 and 65 was favored in 85.7% (Black) and 61.8% (non-Black) of model iterations at a $100 000/QALY gained willingness-to-pay threshold. ConclusionsWhen considering the societal costs of pneumococcal disease, PCV20 at ages 50 and 65 years in the general US population is a potentially economically viable strategy, particularly in Black cohorts.

Adult non-invasive pneumococcal pneumonia in Portugal is dominated by serotype 3 and non-PCV13 serotypes 3-years after near universal PCV13 use in children.

Non-invasive pneumococcal pneumonia (NIPP) is possibly the most frequent infection by Streptococcus pneumoniae in adults. However, the herd effect of vaccinating children in adult NIPP (aNIPP) remains poorly characterized. We determined the serotype distribution and antimicrobial susceptibility of isolates causing aNIPP (>18 years) in 2016-2018 in Portugal; 3 years with near universal vaccination of children with the 13-valent conjugate vaccine (PCV13), following over a decade of significant PCV use in children in the private market. Among the 1,149 aNIPP isolates, the most frequent serotypes detected were: 3 (n = 168, 14.6%), 11A (n = 102, 8.9%), 19F (n = 70, 6.1%), 23A and 23B (n = 62, 5.4% each), 9N (n = 60, 5.2%), 8 and 29/35B (n = 43, 3.7% each); together accounting for 53% of all isolates. The serotype distribution causing aNIPP was stable in 2016-2018, with the serotypes included in PCV7 still being important causes of disease and serotype 3, a PCV13 serotype, remaining the leading cause of aNIPP. There was an increase in penicillin non-susceptibility from 17% in 2016 to 24% in 2018 (p = 0.018). Some PCV13 serotypes, such as 14, 19A and 19F were associated to resistance, which may have contributed to their persistence. The fact that close to 20% of aNIPP is caused by four non-vaccine serotypes (23A, 23B, 9N, and 29/35B) and that there were significant differences in serotype distribution relative to invasive disease, stress the importance of maintaining the surveillance of these infections. The lack of a continued herd effect from vaccinating children and the significant fraction of aNIPP potentially preventable by PCV13 (30%), PCV15 (34%), PCV20 (53%) and the 23-valent polysaccharide vaccine (61%) underscore the importance of considering the broader use of pneumococcal vaccines in adults.

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 & Co.: Grant/Research Support

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.

Distribution of serotypes causing invasive pneumococcal disease in older adults from high-income countries and impact of pediatric and adult vaccination policies

BackgroundNeither indirect protection through use of 13-valent and 10-valent pneumococcal conjugate vaccines (PCV13 and PCV10) in pediatric National Immunization Programs (NIPs) nor direct vaccination with the 23-valent polysaccharide vaccine have eliminated vaccine serotype invasive pneumococcal disease (IPD) in older adults. Vaccinating older adults with higher-valency PCV15 and PCV20 could address remaining IPD due to pediatric PCV serotypes plus additional IPD due to serotypes included in these vaccines. MethodsWe collected serotype-specific IPD data in older adults (≥65 years in most countries), from national or regional surveillance systems or hospital networks of 33 high-income countries. Data were from official government websites, online databases, surveillance system reports, published literature, and personal communication with in-country investigators. Average percentages of IPD serotypes were calculated. ResultsAmong 52,905 cases of IPD with a serotype identified, PCV13 serotypes accounted for 33.7% of IPD (55.8% and 30.6% for countries with PCV10 and PCV13 in the pediatric NIP), most commonly serotypes 3 (14.9%) and 19A (7.0%). PCV15 and PCV20 would cover an additional 10.4% and 32.9% of older adult IPD beyond PCV13 serotypes (PCV10 countries: 7.7% and 23.3%; PCV13 countries: 10.6% and 34.6%). The most common of these additional serotypes were 8 (9.9%), 22F (7.9%), 12F (4.6%), and 11A (3.3%). PPSV23 policies for older adults were not correlated with lower IPD percentages due to PPSV23 serotypes. ConclusionsVaccinating older adults with higher-valency PCVs, especially PCV20, could substantially reduce the remaining IPD burden in high-income countries, regardless of current PCV use in pediatric NIPs and adult PPSV23 policies.

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan

ObjectivesIt is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. MethodsWe determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. ResultsVaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. ConclusionThe progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

Immunogenicity of the 13-Valent Pneumococcal Conjugated Vaccine Followed by the 23-Valent Polysaccharide Vaccine in Chronic Lymphocytic Leukemia.

Patients with Chronic Lymphocytic Leukemia (CLL) have a 29- to 36-fold increased risk of invasive pneumococcal disease (IPD) compared to healthy adults. Therefore, most guidelines recommend vaccination with the 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by the 23-valent polysaccharide vaccine (PPSV23). Because both CLL as well as immunosuppressive treatment have been identified as major determinants of immunogenicity, we aimed to assess the vaccination schedule in untreated and treated CLL patients. We quantified pneumococcal IgG concentrations against five serotypes shared across both vaccines, and against four serotypes unique to PPSV23, before and eight weeks after vaccination. In this retrospective cohort study, we included 143 CLL patients, either treated (n = 38) or naive to treatment (n = 105). While antibody concentrations increased significantly after vaccination, the overall serologic response was low (10.5%), defined as a ≥4-fold antibody increase against ≥70% of the measured serotypes, and significantly influenced by treatment status and prior lymphocyte number. The serologic protection rate, defined as an antibody concentration of ≥1.3 µg/mL for ≥70% of serotypes, was 13% in untreated and 3% in treated CLL patients. Future research should focus on vaccine regimens with a higher immunogenic potential, such as multi-dose schedules with higher-valent T cell dependent conjugated vaccines.

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.

Cost-effectiveness of pneumococcal vaccination among patients with chronic heart failure

Aim To analyze the cost-effectiveness of pneumococcal vaccination in 40- and 65-year-old patients with chronic heart failure (CHF).Material and methods Analysis was performed by Markov modeling from the perspective of the healthcare system. The evaluation was based on Russian epidemiological data taking into account results of international studies. The analyzed schedule of vaccination included one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent polysaccharide vaccine (PPSV23) after one year and vaccination with only one dose of PCV13. The time horizon of the study was 5 years. Costs and life expectancy were discounted at 3.5% per year.Results The cost-effectiveness of vaccination for both 65-year-old and 40-year-old CHF patients is very high: the incremental cost of one additional QALY (Quality-Adjusted Life Year) for PCV13+PPSV23 vaccination is 113.24 thousand rubles, while vaccination with PCV13 entails a reduction in costs by 556.50 rubles per one vaccinated patient. For vaccination of 40-year-old CHF patients with PCV13+PPSV23, the incremental costs per 1 QALY will be 519.72 thousand rubles, while for vaccination with PCV13 it will be 99.33 thousand rubles.Conclusion Pneumococcal vaccination of CHF patients reduces the associated morbidity and mortality and is highly cost effective.

Pneumococcal bacteraemia in adults over a 10-year period (2011-2020): a clinical and serotype analysis.

Streptococcus pneumoniae (pneumococcus) is a human nasopharyngeal tract coloniser responsible for invasive pneumococcal disease, which is largely vaccine preventable. Vaccination is recommended from birth for all, and through adulthood for those with risk conditions. To describe the clinical and serotype analysis of pneumococcus bacteraemia over a 10-year period. A 10-year (February 2011-December 2020) retrospective review was performed on all adult (age ≥18 years) pneumococcus bacteraemia presenting to the four public hospitals in Western Sydney, Australia. Comorbidities and risk factors were recorded. Three hundred unique episodes of S. pneumoniae bloodstream infection (SPBI) were identified during the study period. The median age for SPBI was 63 years with 31.7% aged 70 years or older. A 94.7% had one or more risks factors for SPBI. Pneumonia was reported in 80% of all SPBI, whereas meningitis was reported in 6% and infective endocarditis in <1%. Asplenia was noted in 2.4%. Seven- and 30-day mortality was 6.6% and 11.9%, with a higher 30-day mortality in those aged ≥70 years (24.4%). The serotype distribution showed 7-valent conjugate vaccine covered 11.0% of all isolates, whereas 13-valent conjugate vaccine (13vPCV) and a 23-valent polysaccharide vaccine (23vPPV) covered 41.7% and 69.0% respectively. Immunisation details were available for 110 individuals, of whom, only 7.3% had received pneumococcal vaccination. Most patients with pneumococcal bacteraemia had age- or comorbidity-related risk factors but were not vaccinated. Two-thirds of cases occurred in people aged <70 years. 13vPCV and 23vPPV covered 41.7% and 69.0% of bacteraemic isolates.

Control and Prevention of Invasive Pneumococcal Disease: A Current and Historical Perspective.

Although significant progress has been made in reducing the incidence of invasive pneumococcal disease (IPD) in children, IPD remains a continued threat. Since the introduction of pneumococcal conjugate vaccines (PCVs), rates of IPD and non-IPD have substantially decreased. However, serotype replacement reversed some of the benefits of PCV7 and, more recently, PCV13. Several replacement serotypes are antibiotic resistant, which is a cause of concern for providers. The introduction of the higher-valency conjugate vaccines PCV15 and PCV20 is expected to provide greater serotype coverage; unfortunately, these vaccines do not include some of the recently emerged serotypes. Recommendations for the use of the 23-valent polysaccharide vaccine in high-risk populations may be modified because of the effectiveness of the newer PCVs. Pediatricians must be aware of the new vaccine strategies for the prevention of IPD and the manifestations of IPD so that prompt empirical therapy can be initiated when treatment is required. [Pediatr Ann. 2023;52(3):e96-e101.].

Impact of vaccination with pneumococcal vaccines on recurrent pneumonia in patients with chronic obstructive pulmonary disease

Community-acquired pneumonia (САР) and chronic obstructive pulmonary disease (COPD) are among the main causes of mortality worldwide, and, in addition, they also lead to great economic losses for the health system of all countries. Currently, there is an increase in cases of recurrent pneumonia, both in the general population and, in particular, in patients with COPD. One of the most important risk factors for the development of pneumonia is the previous episode of САР. Potential risk factors for recurrent pneumonia are concomitant diseases such as heart failure, COPD, diabetes mellitus, neurological disorders, swallowing dysfunction, immune deficiency. To conduct a retrospective analysis of the effect of vaccine prophylaxis with conjugated pneumococcal vaccine (PCV13) and polysaccharide pneumococcal vaccine (PPV23) on the risk of recurrent pneumonia in patients with COPD. A total of 302 male patients were included in the retrospective study. When analyzing the data, the fact of the development of pneumonia of any etiology during the 5th observation period was taken into account. For the recurrence of pneumonia, more than two episodes of CAP were taken during the year. 13-valent conjugated pneumococcal vaccine Prevenar-13 and 23-valent polysaccharide vaccine Pneumo23 were used for vaccine prophylaxis. The relative risk of the event was calculated. A 95% confidence interval was used. A retrospective analysis showed that, firstly, CAP is a fairly frequent complication of COPD: initially, the average percentage of cases of САР was 19.3%. Secondly, the risk of developing repeated episodes of pneumonia remains quite high in unvaccinated patients and tends to increase within 5 years: from 17 to 22%. Thirdly, the pneumococcal vaccines used have different effects on the risk of recurrent pneumonia in patients with COPD, a significant decrease in the number of recurrent pneumonia is observed only with the use of conjugated vaccines.

Cost-Effectiveness of Pneumococcal Vaccination among Patients with Diabetes Mellitus

Relevance. Patients with diabetes mellitus have an increased risk of developing various infections, including those of the lower respiratory tract. Immunization with anti-pneumococcal vaccines reduces pneumonia-related hospitalizations and deaths.Aim. Evaluate the cost-effectiveness of vaccination against pneumococcal infection in 40and 65-year-old patients with type 2 diabetes mellitus (DM2).Material and methods. The analysis was carried out from the perspective of the healthcare system. The Markov model based on Russian epidemiological data, taking into account the results of foreign studies, was used. Vaccination schedules with 1 dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 1 dose of pneumococcal 23-valent polysaccharide vaccine (PPV23) and vaccination with only 1 dose of PCV13 were evaluated. The time horizon of the study is 5 years. Costs and life expectancy were discounted by 3.5% per year.Results. Vaccination of 65-year-old patients with type 2 diabetes is characterized by extremely high cost-effectiveness (the incremental cost effectiveness ratio – ICER – for PCV13+PPV23 vaccination is 189.27 thousand rubles/QALY, and PCV13 vaccination entails a cost reduction of 371.92 rubles per 1 vaccinated). When vaccinating 40-year-old patients, the ICER for PCV13 + PPV23 vaccination is 491.31 thousand rubles/QALY, and for PCV13 – 55.31 thousand rubles/QALY.Conclusion. Vaccination against pneumococcal disease in 40and 65-year-old patients with DM2 reduces the associated morbidity and mortality and is highly cost-effective. Compared to PCV13 vaccination alone, vaccination with PCV13 followed by the introduction of PPV23 provides an increase in the number of prevented cases of the disease and the deaths caused by it, but at the same time requires additional costs.

Immunogenicity of the Currently Recommended Pneumococcal Vaccination Schedule in Patients with Chronic Lymphocytic Leukaemia

Background Patients with chronic lymphocytic leukemia (CLL) are at increased risk of both invasive pneumococcal disease (IPD) and community acquired pneumonia (CAP) caused by Streptococcus pneumoniae. Therefore, international guidelines recommend pneumococcal vaccination for all CLL patients, preferably before initiation of treatment. The vaccination schedule recommended in the European Conference on Infections in Leukaemia (ECIL) 7 guideline consists of Prevnar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23®, a 23-valent polysaccharide vaccine (PPSV23). However, the immunogenicity of this sequential pneumococcal vaccination schedule in CLL patients is unknown. The aim of this study is to assess the immunogenicity of PCV13 followed by PPSV23 in untreated and treated CLL patients, as CLL treatment has been shown to be a major determinant of COVID-19 vaccine immunogenicity. Methods We quantified pneumococcal immunoglobulin G (IgG) concentrations to 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F) and 4 serotypes unique to PPSV23 (8, 15B, 20, 33F) before and 4-8 weeks after vaccination using a validated multiplex immunoassay, Luminex®. The primary outcome was the serologic response rate (SRR), defined as a ≥4-fold increase in ≥70% of the serotype-specific anti-pneumococcal IgGs. Secondary outcome was serologic protection, defined as an antibody concentration of ≥1.3 mcg/ml for ≥70% of all measured serotypes, in accordance with the definition by the American Academy of Allergy, Asthma & Immunology. Additional secondary outcomes were serotype-specific serologic protection and IgG level dynamics. Results We included 113 CLL patients (mean age 66 years; 39/113 female) in one academic and six teaching hospitals in the Netherlands. All completed the vaccination and measurement schedule. Median time since CLL diagnosis was 3.6 years. Of the 113 patients 33 had previously received CLL treatment, including rituximab (22 patients), cytotoxic chemotherapy (11), ibrutinib (10) and/or venetoclax (7). Seven patients received intravenous immunoglobulin prior to the vaccinations, while 6 received this during the vaccination scheme. The SRR was 11.5% (15% in untreated and 3% in treated patients) (Table 1). A statistically significant increase in all serotype-specific antibody concentrations was observed after vaccination (p <0.001) (Figure 1). The immunogenicity varied per serotype: the percentage of patients mounting a 4-fold increase was lowest for serotype 20 (16%) and highest for serotype 9V (40%). The serotype-specific anti-pneumococcal IgGs after vaccination were all significantly lower in treated than in previously untreated patients. Nevertheless, treatment status was not statistically significant associated with the SRR. Total IgG concentration prior to vaccination was the only evaluated factor associated with the SRR (OR 5.69; p = 0.008). Serologic protection increased from 1.8% before vaccination to 10.6% after both vaccinations (13.8% in untreated and 3% in treated patients). Serotype-specific protection was highest for serotype 14 and 33F (43.4% of patients obtained a concentration of ≥1.3 mcg/ml) and lowest for serotype 6B (16.8%). Conclusion The serologic response to combined PCV13 and PPSV23 vaccination is impaired in previously treated CLL patients as well as in treatment-naive patients, a contrast with COVID-19 vaccination. These findings emphasize the importance of further investigation into the pneumococcal vaccination response in CLL patients. Since patients with CLL are insufficiently protected after a single dose of PCV13, research should focus on multi-dose PCV schedules with the currently available higher valent T cell dependent conjugate vaccines. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Immunogenicity of a 20-valent pneumococcal conjugate vaccine in adults 18 to 64 years old with medical conditions and other factors that increase risk of pneumococcal disease

ABSTRACT The aim of this post hoc analysis was to describe the immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adults with chronic medical conditions or smoking that place them at increased risk of developing pneumococcal disease. Data from 2 phase 3, randomized, active-controlled, double-blind studies in pneumococcal vaccine-naive adults were analyzed. Study 1: adults ≥18 years were enrolled in 1 of 3 age-based cohorts (18‒49, 50‒59, and ≥60 years) and randomized (1:1, adults ≥60 years; 3:1, younger cohorts) to receive 1 dose of PCV20 or 13-valent PCV (PCV13). Participants ≥60 years who received PCV13 were administered 23-valent polysaccharide vaccine 1 month later. Study 2: adults 18‒49 years were randomized (2:2:2:1) to receive 1 dose of PCV20 from 1 of 3 lots or PCV13. Opsonophagocytic activity (OPA) titers were measured in sera collected before and 1 month after vaccination. We investigated immune responses of PCV20 among participants 18‒64 and 18‒49 years of age with ≥1 medical condition or other factor (smoking) that increases the risk of serious pneumococcal disease. Of 4369 participants overall (PCV20, n = 2975; PCV13, n = 1394), 1329 participants (30%) had ≥1 risk factor; most commonly smoking, diabetes, and chronic pulmonary disease. Among participants with risk factors, substantial increases in OPA geometric mean titers were observed across the 20 vaccine serotypes from before vaccination to 1 month after PCV20. Robust immune responses to all 20 vaccine serotypes 1 month after PCV20 were observed in adults with increased risk of serious pneumococcal disease. Clinical trial registration NCT03760146, NCT03828617.

A comprehensive overview of pneumococcal vaccination recommendations for adults in South Africa, 2022.

Pneumococcal infections remain a common global cause of significant morbidity and mortality. The first recommendations for adult pneumococcal vaccination, published in South Africa in 1999, contained information only on the 23-valent polysaccharide vaccine (PPV23). With the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) for use in adults and the perceived uncertainty that most clinicians had regarding use of these vaccines in adults, these vaccine recommendations were updated in 2022. A Working Group, which consisted of individuals in various fields of medical practice in South Africa, who were from different areas of the country, and included clinicians from both the public and private sectors, was assembled to revise the recommendations. The expertise of the participants varied widely, dependent on their training and specialty, and encompassed different organ systems, disease conditions, and/or practice types. Each participant was allocated a different section, based on their expertise, for which they were required to do an extensive review of the current literature and write their section. The entire working group then reviewed the complete document several times, following additional comments and recommendations. This update contains recommendations for the use of both PPV23 and PCV13, either alone, or in sequence, both in vaccine naïve and in previously vaccinated individuals. It includes both age and risk categories, and encompasses the elderly (≥65 years), as well as younger adults (<65 years) with comorbid conditions or with high-risk conditions and/or immunocompromise. It is hoped that this review and its associated vaccine recommendations will clarify for clinicians, from all spheres of practice in South Africa, how, where, and when pneumococcal vaccines should be used in adults, with the ultimate goal of significantly increasing the appropriate use of these vaccines, in order to decrease the substantial morbidity and mortality associated with pneumococcal infections in adults in South Africa. Furthermore, it is hoped that this review of local epidemiological data and the manner in which this information was interpreted in the development of these local vaccine recommendations, could be used as an example for other regions of the world, to tailor their recommendations to locally available epidemiological data.

Cost-utility analysis of a universal pneumococcal vaccination programme for older adults in Norway

ABSTRACT The aim of this study was to establish whether a universal pneumococcal vaccination for older adults in Norway is likely to be cost-effective from the perspective of the health care provider. A decision tree model developed by the Public Health Agency of Sweden was adopted to the Norwegian setting. Two cohorts, consisting of 65-year-olds and 75-year-olds grouped into vaccinated and unvaccinated, were followed over a 5-year time horizon. In the base case, the 23-valent polysaccharide vaccine (PPV23) was used while the 13-valent pneumococcal conjugate vaccine (PCV13) was included in scenario analyses only. The costs and health benefits (measured in quality adjusted life years (QALY) gained) were compared in the two cohorts between the vaccinated and unvaccinated groups. The impact of indirect effects of the vaccine, such as herd immunity and serotype replacement, were not investigated. The relative importance of change in price was assessed by performing one-way sensitivity analyses. Under base-case assumptions, the programme for the 75-year-old cohort is expected to be cost-effective from the health care perspective at the current pharmacy purchasing price and at 75% vaccination coverage as it falls below the lower end of the cost-effectiveness threshold range (NOK 9467/EUR 964). In comparison, for the 65-year-old cohort the cost per QALY gained is approximately NOK 780 206 (EUR 79 451) under the base-case assumptions which falls within the acceptable ranges in a Norwegian context for both the 65- and 75-year-old cohorts. There is no exact cost-effectiveness threshold in Norway. However, introducing a vaccination programme against pneumococcal disease for 65-year-olds and 75-year-olds in Norway is likely to fall within the acceptable cost-effectiveness threshold range.

Cost-Effectiveness of Newly Recommended Pneumococcal Vaccination Strategies in Older Underserved Minority Adults in the USA.

IntroductionUS pneumococcal vaccination recommendations for adults aged 65 years or older recently changed, with options for either 20-valent pneumococcal conjugate vaccine (PCV20) or the combination of 15-valent conjugate vaccine (PCV15) followed by 23-valent polysaccharide vaccine (PPSV23) 1 year later. Underserved minority adults are at higher risk for pneumococcal disease.MethodsA Markov decision analysis model estimated the incremental cost-effectiveness of the newly adopted general population pneumococcal vaccination strategies in older underserved minority adults. The model examined hypothetical 65-year-old US Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts receiving PCV20 or PCV15/PPSV23, or no vaccination. Main outcome measures included incremental cost-effectiveness per quality-adjusted life year (QALY) gained and pneumococcal disease public health outcomes.ResultsBlack cohorts had a greater risk of pneumococcal disease hospitalization compared to non-Black cohorts. In Black cohorts, total per person PCV20 strategy costs, compared to no vaccination, were $124 higher while gaining 0.00073 QALY, or $169,540/QALY gained. PCV15/PPSV23 cost $535,797/QALY compared to PCV20. In the non-Black cohort, PCV20 cost $210,529/QALY gained compared to no vaccination and PCV15/PPSV23 cost $728,423/QALY. Plausible variation of vaccine effectiveness minimally affected PCV20 strategy results and made PCV15/PPSV23 more unfavorable. In scenarios where the simpler one-vaccine PCV20 strategy increased absolute vaccine uptake by 10%, PCV20 cost-effectiveness changed minimally while PCV15/PPSV23 cost in excess of $6 million/QALY in the Black cohort. In probabilistic sensitivity analyses that varied all parameters simultaneously, PCV15/PPSV23 was unlikely to be favored at thresholds less than $500,000/QALY gained.ConclusionGeneral population recommendations for PCV20 use are substantially more economically reasonable in Black and non-Black older adult populations than PCV15/PPSV23. If using a single vaccine increases uptake, which is potentially more likely in the underserved, then PCV20 use becomes even more favorable.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00669-x.

Continued Vaccine Breakthrough Cases of Serotype 3 Complicated Pneumonia in Vaccinated Children, Portugal (2016-2019).

ABSTRACTWe previously reported that despite the use of pneumococcal conjugate vaccines (PCVs), vaccine serotypes remained important causes of pneumonia with pleural effusion and empyema (pediatric complicated pneumococcal pneumonia [PCPP]). We cultured and performed PCR on 174 pleural fluid samples recovered from pediatric patients in Portugal from 2016 to 2019 to identify and serotype Streptococcus pneumoniae. Most PCPP cases (n = 87/98) were identified by PCR only. Serotypes 3 (67%), 14, and 8 (5% each) were the most frequent. Vaccine breakthrough cases were seen among age-appropriately, 13-valent, PCV vaccinated children (median: 3 years, range: 17 months to 7 years), mostly with serotype 3 (n = 27) but also with serotypes 14 and 19A (n = 2 each). One breakthrough was seen with serotype 14 in an age-appropriately, 10-valent, PCV-vaccinated child and another with serotype 3 in a child to whom the 23-valent polysaccharide vaccine was administered. While the relative risk of serotype 1 PCPP decreased almost 10-fold from the period of 2010 to 2015 to the period of 2016 to 2019 (relative risk [RR] = 0.106), that of serotype 3 PCPP almost doubled (RR = 1.835). Our data highlight the importance of molecular diagnostics in identifying PCPP and document the continued importance of serotype 3 PCPP, even when PCV13 use with almost universal coverage could be expected to reduce exposure to this serotype.IMPORTANCE The use of conjugate vaccines against Streptococcus pneumoniae in children has led to substantial reductions in pneumococcal invasive disease. However, the reductions seen in each of the 13 serotypes currently included in the highest-valency vaccine approved for use in children (PCV13), were not the same. It is becoming clear that most vaccine breakthroughs worldwide involve serotype 3 and are frequently associated with complicated pneumonia cases, often with empyema or pleural effusion. Here, we show that despite almost universal PCV13 use, which would be expected to reduce vaccine serotype circulation and further reinforce vaccine direct protection, pneumococci and serotype 3 remain the major causes of pediatric complicated pneumonia. Molecular methods are essential to identify and serotype pneumococci in these cases, which frequently reflect vaccine breakthroughs. A broader use of molecular diagnostics will be essential to determine the role of this important serotype in the context of PCV13 use in different geographic regions.