Current Pneumococcal Vaccines Research Articles

Immunization with recombinant Streptococcus pneumoniae PgdA protects mice against lung invasion.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro. Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines.

Changes in the cost-effectiveness of pneumococcal vaccination and of programs to increase its uptake in U.S. older adults.

Multiple factors, such as less complex U.S. adult pneumococcal recommendations that could increase vaccination rates, childhood pneumococcal vaccination indirect effects that decrease adult vaccination impact, and increased vaccine hesitancy (particularly in underserved minorities), could diminish the cost-effectiveness of programs to increase pneumococcal vaccination in older adults. Prior analyses supported the economic favorability of these programs. A Markov model compared no vaccination and current recommendations (either 20-valent pneumococcal conjugate vaccine [PCV20] alone or 15-valent pneumococcal conjugate vaccine plus the 23-valent pneumococcal polysaccharide vaccine [PCV15/PPSV23]) without or with programs to increase vaccine uptake in Black and non-Black 65-year-old cohorts. Pre-pandemic population- and serotype-specific pneumococcal disease risk and illness/vaccine costs came from U.S. Program costs were $2.19 per vaccine-eligible person and increased absolute vaccination likelihood by 7.5%. Delphi panel estimates and trial data informed vaccine effectiveness values. Analyses took a healthcare perspective, discounting at 3%/year over a lifetime time horizon. Uptake programs decreased pneumococcal disease overall. In Black cohorts, PCV20 without program cost $216,805 per quality-adjusted life year (QALY) gained compared with no vaccination; incremental cost-effectiveness was $245,546/QALY for PCV20 with program and $425,264/QALY for PCV15/PPSV23 with program. In non-Black cohorts, all strategies cost >$200,000/QALY gained. When considering the potential indirect effects from childhood vaccination, all strategies became less economically attractive. Increased vaccination with less complex strategies had negligible effects. In probabilistic sensitivity analyses, current recommendations with or without programs were unlikely to be favored at thresholds <$200,000/QALY gained. Current U.S. pneumococcal vaccination recommendations for older adults were unlikely to be economically reasonable with or without programs to increase vaccine uptake. Alternatives to current pneumococcal vaccines that include pneumococcal serotypes associated with adult disease should be considered.

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.

Pneumococcal Perplexity: Improving Awareness of Updated Pneumococcal Vaccination Recommendations in Two Large Military Treatment Facilities.

Vaccinations are an essential aspect of preventive medicine. In October 2021, the pneumococcal conjugate vaccine-20 (PCV-20) and PCV-15 were authorized for use in adults by the U.S. FDA. In 2022, the Advisory Committee on Immunization Practices (ACIP) subsequently published updated pneumococcal vaccination recommendations that incorporate both PCV-20 and PCV-15. Pneumococcal vaccination is effective in reducing pneumococcal disease, particularly in high-risk patient groups such as those with chronic lung disease; however, the updated dosing schedule for pneumococcal vaccinations can be quite confusing, especially if patients have previously received "older" vaccinations, such as pneumococcal polysaccharide vaccine-23 or PCV-13. The purpose of this quality improvement project was to increase providers' knowledge of current ACIP pneumococcal vaccination recommendations, including indications and dosing schedule, and to improve pneumococcal vaccination rates among eligible adults and children. Focused education sessions were presented to primary care and subspecialty residents, fellows, and staff at Brooke Army Medical Center and Wilford Hall Ambulatory Surgical Center regarding current ACIP pneumococcal vaccination recommendations. Sessions included information about PCV-15 and PCV-20 vaccines, indications for vaccination, and dosing schedules. Subjective knowledge of updated ACIP pneumococcal vaccination recommendations was assessed among primary care and subspecialty residents, fellows, and staff via an anonymous survey both pre- and post-intervention. Number of PCV-20 vaccinations given and estimated vaccination rates of patients aged 19 to 64 years with asthma were assessed pre- and post-intervention over a 6 month time span. Of surveyed providers, only 9% discussed vaccinations at every visit and 11% did not discuss vaccinations at all. There was a statistically significant increase in providers' knowledge of pneumococcal vaccination guidelines for children post-intervention (P = .01) but no statistically significant increase in knowledge for guidelines for adults, for patients that have received prior pneumococcal vaccines, or in overall confidence in recommending pneumococcal vaccines. There was a 17% increase in the number of PCV-20 vaccinations given post-intervention (198 pre-intervention, 232 post-intervention). The estimated PCV-20 vaccination rate for adults aged 19 to 64 years with asthma increased from 14.9% pre-intervention to 19.5% post-intervention (P = .33). There is a significant knowledge gap regarding ACIP pneumococcal vaccination recommendations among military providers and a low pneumococcal vaccination rate for adults aged 19 to 64 years with asthma at Joint Base-San Antonio MTFs. Focused education sessions were effective in increasing providers' knowledge of updated pneumococcal vaccination recommendations, confidence in recommending vaccines, total number of pneumococcal vaccinations given, and estimated pneumococcal vaccination rate for adults with asthma. The validity of conclusions drawn from our data were limited because of discordant numbers of survey respondents as well as potentially inaccurate estimates of pneumococcal vaccination rates pre- and post-intervention. Despite this, the results warrant continued education of pneumococcal vaccines, indications, and dosing schedules.

General Practitioners' Awareness and Perception of Current Pneumococcal Vaccination for Adult Patients with Known Risk Factors in Switzerland: Evidence from a Survey.

In Switzerland, the National Immunization Advisory Group (NITAG) has formulated recommendations for pneumococcal vaccination among adult risk patients. Little is known about general practitioners' (GPs') perception, knowledge, and implementation of these recommendations. Therefore, we investigated GPs' awareness and drivers of and barriers to pneumococcal vaccination using a cross-sectional web-based survey of GPs. Of the 300 study participants, 81.3% were aware of the recommendations for vaccinating at-risk adult patients, but only 42.7% were aware of all risk groups. The recommendations were perceived by 79.7% as slightly to very complex. Most GPs (66.7%) had good arguments to convince patients to get vaccinated, but only 41.7% reported recognizing patients at risk for pneumococcal disease, and only 46.7% checked their patients' vaccination status and proposed vaccination if needed. The main reasons for not vaccinating were patients' refusal (80.1%), lack of reimbursement by the health insurance (34.5%), patients' fear of side effects (25.1%), and lack of regulatory approval despite the NITAG recommendations (23.7%). Most (77.3%) agreed that the treating chronic disease specialist should recommend the vaccination and 94.7% believed that adult-risk patients would not be aware of their need for pneumococcal vaccinations. Optimal implementation of the recommendations will require addressing knowledge gaps and reported barriers.

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults

IntroductionCDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear. MethodsA Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined. ResultsIn the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios. ConclusionAn in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults.

Penicillin-binding protein genotyping of penicillin-nonsusceptible Streptococcus pneumoniae isolates from the nasopharynx of healthy preschool children

Abstract Streptococcus pneumoniae is one of the most frequent bacterial identified causes of community-acquired pneumonia, otitis media and meningitis. It is, as well, a common cause of bacteraemia’s significant morbidity and mortality. Beta-lactam antibiotics (BLAs) are the first line of empirical treatment for pneumococcal infections. The targets of BLAs are penicillin-binding proteins (PBPs), the modifications of which are one of the reasons why pneumococci are non-susceptible to BLAs. In our work, a total of 39 Streptococcus pneumoniae isolates were obtained from 176 healthy children, both vaccinated and non-vaccinated. The isolates were tested for antimicrobial susceptibility, and their penicillin-binding proteins (PBPs) were typed by the restriction fragment length of the polymorphism analysis of their pbp genes. The most frequent serotypes among the penicillin non-susceptible Streptococcus pneumoniae (PNSSP) isolates were 23B, 35B and 19F. Restriction enzyme analyses of pbp1a, pbp2b, and pbp2x genes revealed 5, 3 and 3 different patterns, respectively, and a total of 4 different PBPs profiles of PNSSP isolates belonging to serotypes not included in pneumococcal conjugate vaccines were demonstrated. We conclude that the level of resistance should be monitored constantly to ascertain the effect of current pneumococcal conjugate vaccines, as well as to recognize new circumstances developing in Poland, as well as the possibility of multiple, independent imports of resistant strains from abroad.

Memory Th17 cell-mediated protection against lethal secondary pneumococcal pneumonia following influenza infection.

Streptococcus pneumoniae (Sp) frequently causes secondary pneumonia after influenza A virus (IAV) infection, leading to high morbidity and mortality worldwide. Concomitant pneumococcal and influenza vaccination improves protection against coinfection but does not always yield complete protection. Impaired innate and adaptive immune responses have been associated with attenuated bacterial clearance in influenza virus-infected hosts. In this study, we showed that preceding low-dose IAV infection caused persistent Sp infection and suppression of bacteria-specific T-helper type 17 (Th17) responses in mice. Prior Sp infection protected against subsequent IAV/Sp coinfection by improving bacterial clearance and rescuing bacteria-specific Th17 responses in the lungs. Furthermore, blockade of IL-17A by anti-IL-17A antibodies abrogated the protective effect of Sp preinfection. Importantly, memory Th17 responses induced by Sp preinfection overcame viral-driven Th17 inhibition and provided cross-protection against different Sp serotypes following coinfection with IAV. These results indicate that bacteria-specific Th17 memory cells play a key role in providing protection against IAV/Sp coinfection in a serotype-independent manner and suggest that a Th17-based vaccine would have excellent potential to mitigate disease caused by coinfection. IMPORTANCE Streptococcus pneumoniae (Sp) frequently causes secondary bacterial pneumonia after influenza A virus (IAV) infection, leading to increased morbidity and mortality worldwide. Current pneumococcal vaccines induce highly strain-specific antibody responses and provide limited protection against IAV/Sp coinfection. Th17 responses are broadly protective against Sp single infection, but whether the Th17 response, which is dramatically impaired by IAV infection in naïve mice, might be effective in immunization-induced protection against pneumonia caused by coinfection is not known. In this study, we have revealed that Sp-specific memory Th17 cells rescue IAV-driven inhibition and provide cross-protection against subsequent lethal coinfection with IAV and different Sp serotypes. These results indicate that a Th17-based vaccine would have excellent potential to mitigate disease caused by IAV/Sp coinfection.

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Community-Acquired Pneumonia Incidence in Adults Aged 18 Years and Older in Goto City, Japan: A Prospective Population-Based Study

Reanalysis of the Clinical and Economic Burden of Pneumococcal Disease Due to Serotypes Contained in Current and Investigational Pneumococcal Conjugate Vaccines in Children < 5 Age: A Societal Perspective.

Studies that estimate the economic burden of pediatric pneumococcal disease often only report direct medical costs and omit indirect non-medical costs. Given these indirect costs are not included in most calculations, the full economic burden attributable to pneumococcal conjugate vaccine (PCV) serotypes is often underestimated. This study seeks to quantify the full broader economic burden of pediatric pneumococcal disease associated with PCV serotypes. We conducted a reanalysis of a previous study where non-medical costs associated with caregiving for a child with pneumococcal disease are considered. The annual indirect non-medical economic burden attributed to PCV serotypes was subsequently calculated for 13 countries. We included five countries with 10-valent (PCV10) national immunization programs (NIPs) (Austria, Finland, The Netherlands, New Zealand, and Sweden) and eight countries with 13-valent (PCV13) NIPs (Australia, Canada, France, Germany, Italy, South Korea, Spain, and the UK). Input parameters were derived from published literature. Indirect costs were inflated to 2021 values in US dollars (USD). The total annual indirect economic burden associated with pediatric pneumococcal diseases attributable to PCV10, PCV13, the 15-valent (PCV15), and the 20-valent (PCV20) serotypes were $46.51million, $158.95million, $223.00million, and $413.97 million, respectively. The five countries with PCV10 NIPs bear a greater societal burden associated with PCV13 serotypes, whereas the residual societal burden in the eight countries with PCV13 NIPs was primarily attributable to non-PCV13 serotypes. The inclusion of non-medical costs nearly tripled the total economic burden compared with only including direct medical costs estimated from a previous study. The results from this reanalysis can help inform decision-makers on the broader economic societal burden associated with PCV serotypes and the need for higher-valent PCVs.

Optimization of Elderly Influenza and Pneumococcal Immunization Programs in Beijing, China Using Health Economic Evaluations: A Modeling Study.

(1) Background: Currently, residents ≥ 60 and ≥65 years old in Beijing, China, are eligible for free influenza and pneumococcal polysaccharide vaccines (PPSV23), respectively. The present study aimed to assess the cost-effectiveness of current and alternative strategies of dual influenza and PPSV23 vaccination among the elderly in Beijing. (2) Methods: We developed a Markov state-transition model to compare the costs and the quality-adjusted life years (QALYs) associated with four influenza and PPSV23 vaccination strategies among the elderly in Beijing. The strategies were as follows: (1) no vaccination; (2) only flu vaccine for people ≥ 60 years old; (3) flu vaccine for people ≥ 60 years old and PPSV23 for people ≥ 65 years old; and (4) dual influenza vaccines and PPSV23 for people ≥ 60 years old. Incremental costs and QALYs were quantified to determine the optimal option. If dominant strategies emerged, the Chinese gross domestic product per capita in 2021 (80,976 CNY) was used as the willingness-to-pay (WTP) threshold to covert QALYs into the monetary equivalent. (3) Results: The current program saved costs and increased QALYs compared to no vaccination or flu vaccine-only strategies. However, extending free PPSV23 to people ≥ 60 years old saved 0.35 CNY additionally while increasing QALYs marginally compared with the current policy. Results were robust in all sensitivity analyses. (4) Conclusion: Beijing's current dual influenza and pneumococcal vaccination program was cost-effective among the elderly compared with the preceding policies of no vaccination and flu-only immunization programs. However, the program can further save money while enhancing the population health by extending PPSV23 to all people ≥ 60 years old.

Serotype distribution of Streptococcus pneumoniae and pneumococcal vaccine coverage in adults in Turkey between 2015 and 2018

Objective To evaluate the serotype distribution and antibiotic resistance in pneumococcal infections in adults and to provide a perspective regarding serotype coverage of both current and future pneumococcal vaccines. Patients and methods This passive surveillance study was conducted with the Streptococcus pneumoniae strains isolated from the specimens of patients with pneumonia (materials isolated from bronchoalveolar lavage), bacteraemia, meningitis, pleuritis and peritonitis between 2015 and 2018. Serogrouping and serotyping were performed by latex particle agglutination and by conventional Quellung reaction using commercial type-specific antisera, respectively. The strains were analysed for penicillin, cefotaxime, erythromycin and moxifloxacin susceptibilities by E-test. Results In the whole study group (410 samples from adults aged ≥18 years), the most frequent serotypes were 3 (14.1%), 19 F (12%) and 1 (9.3%). The vaccine coverage for PCV13, PCV15, PCV20 and PPV23 was 63.9%, 66.6%, 74.1% and 75.9%, respectively, in all isolates. Penicillin non-susceptibility in invasive pneumococcal disease (IPD) was 70.8% and 57.1% in the patients aged <65 and ≥65 years, respectively. About 21.1% and 4.3% of the patients with and without IPD had cefotaxime resistance. Non-susceptibility to erythromycin and moxifloxacin was 38.2% and 1.2%, respectively. Conclusions The results revealed that novel PCV vaccines may provide improved coverage as compared with the currently available vaccine, PCV13. The significant antibiotic resistance rates imply the need to extend the serotype coverage of the vaccines. Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution and incidence changes of IPD cases in the population and to inform policy makers to make necessary improvements in the national immunization programmes. Key messages This multicentre study demonstrated the most recent serotype distribution and antibiotic resistance in adult population in Turkey. Shifting from PCV13 to novel conjugated vaccines will significantly increase the coverage. Continuing the surveillance in pneumococcal diseases is critical to explore the serotype distribution changes and the incidence of cases with invasive pneumococcal disease in the population.

Cost-effectiveness of using a 20-valent pneumococcal conjugate vaccine to directly protect adults in England at elevated risk of pneumococcal disease

ABSTRACT Objectives Despite the current pneumococcal vaccination program in England for older adults and adults with underlying conditions, disease burden remains high. We evaluated cost-effectiveness of 20-valent pneumococcal conjugate vaccine (PCV20) compared to current pneumococcal recommendations for adults in England. Methods Lifetime outcomes/costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65–99 years and adults aged 18–64 years with underlying conditions in England were projected using a deterministic cohort model. Vaccination with PCV20 was compared with 23-valent pneumococcal polysaccharide vaccine (PPV23) from the National Health Service perspective. Results PCV20 was cost saving compared with PPV23 in base case and most sensitivity analyses. In the base case, replacing PPV23 with PCV20 prevented 7,789 and 140,046 cases of IPD and hospitalized CAP, respectively, and 22,199 associated deaths, resulting in incremental gain of 91,375 quality-adjusted life-years (QALYs) and incremental savings of £160M. In probabilistic sensitivity analyses, PCV20 (vs. PPV23) was cost saving in 85% of simulations; incremental cost per QALY was below £30,000 in 99% of simulations. Conclusions PCV20 vaccination in adults aged 65–99 years and those aged 18–64 years with underlying comorbidities in England is expected to prevent more hospitalizations, save more lives, and yield lower overall costs than current recommendations for PPV23.

Public health and budgetary impact of 20-valent pneumococcal conjugate vaccine for adults in England

ABSTRACT Background Despite use of 23-valent pneumococcal polysaccharide vaccine (PPV23) in England, disease burden among at-risk adults remains high. We evaluated the public health and budgetary impact of 20-valent pneumococcal conjugate vaccine (PCV20) compared to the current adult pneumococcal vaccination program. Methods Five-year outcomes and costs of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP) among adults aged 65–99 years and adults aged 18–64 years with underlying conditions in England were projected using a deterministic cohort model. Hypothetical vaccination with PCV20 versus PPV23 was compared from the National Health Service (NHS) perspective. Results Replacing PPV23 with PCV20 would prevent 785 IPD hospitalizations, 11,751 CAP hospitalizations, and 1,414 deaths over 5 years, and would reduce medical care costs by £48.5 M. With vaccination costs higher by £107.2 M, projected net budgetary impact is £58.7 M. The budgetary impact would be greatest in year 1 (£26.3 M), and would decrease over time (to £1.6 M by year 5). The average budget increase (£11.7 M/year) represents <0.01% of the Department of Health and Social Care total budget and <3% of the vaccine budget. Conclusions Use of PCV20 among adults currently eligible for PPV23 in England would substantially reduce the burden of pneumococcal disease, with modest budgetary impact.

Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004–20: a national surveillance study

BackgroundEpidemiological studies are necessary to explore the effect of current pneumococcal conjugate vaccines (PCVs) against antibiotic resistance, including the rise of non-vaccine serotypes that are resistant to antibiotics. Hence, epidemiological changes in the antimicrobial pattern of Streptococcus pneumoniae before and during the first year of the COVID-19 pandemic were studied.MethodsIn this national surveillance study, we characterised the antimicrobial susceptibility to a panel of antibiotics in 3017 pneumococcal clinical isolates with reduced susceptibility to penicillin during 2004–20 in Spain. This study covered the early and late PCV7 periods; the early, middle, and late PCV13 periods; and the first year of the COVID-19 pandemic, to evaluate the contribution of PCVs and the pandemic to the emergence of non-vaccine serotypes associated with antibiotic resistance.FindingsSerotypes included in PCV7 and PCV13 showed a decline after the introduction of PCVs in Spain. However, an increase in non-PCV13 serotypes (mainly 11A, 24F, and 23B) that were not susceptible to penicillin promptly appeared. A rise in the proportion of pneumococcal strains with reduced susceptibility to β-lactams and erythromycin was observed in 2020, coinciding with the emergence of SARS-CoV-2. Cefditoren was the β-lactam with the lowest minimum inhibitory concentration (MIC)50 or MIC90 values, and had the highest proportion of susceptible strains throughout 2004–20.InterpretationThe increase in non-PCV13 serotypes associated with antibiotic resistance is concerning, especially the increase of penicillin resistance linked to serotypes 11A and 24F. The future use of PCVs with an increasingly broad spectrum (such as PCV20, which includes serotype 11A) could reduce the impact of antibiotic resistance for non-PCV13 serotypes. The use of antibiotics to prevent co-infections in patients with COVID-19 might have affected the increased proportion of pneumococcal-resistant strains. Cefotaxime as a parenteral option, and cefditoren as an oral choice, were the antibiotics with the highest activity against non-PCV20 serotypes.FundingThe Spanish Ministry of Science and Innovation and Meiji-Pharma Spain.TranslationFor the Spanish translation of the abstract see Supplementary Materials section.

PCV13 Vaccination of Adults against Pneumococcal Disease: What We Have Learned from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA).

The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA) evaluated older adult pneumococcal vaccination and was one of the largest vaccine clinical trials ever conducted. Among older adults aged ≥65 years, the trial established 13-valent pneumococcal conjugate vaccine (PCV13) efficacy in preventing first episodes of bacteremic and nonbacteremic pneumococcal vaccine serotype (VT) community acquired pneumonia (CAP), and of vaccine serotype invasive pneumococcal disease (VT-IPD). Since the publication of the original trial results, 15 additional publications have extended the analyses. In this review, we summarize and integrate the full body of evidence generated by these studies, contextualize the results in light of their public health relevance, and discuss their implications for the assessment of current and future adult pneumococcal vaccination. This accumulating evidence has helped to better understand PCV13 efficacy, serotype-specific efficacy, efficacy in subgroups, the interpretation of immunogenicity data, and the public health value of adult PCV vaccination.

Pneumococcal Surface Protein A: A Promising Candidate for the Next Generation of Pneumococcal Vaccines.

Streptococcus pneumoniae is the bacterium that causes pneumococcal disease which often results in pneumonia, meningitis, otitis media, septicemia and sinusitis. Pneumonia, particularly, is a significant cause of worldwide morbidity and a global health burden as well. Treatment often relies on antimicrobials, to which the pathogen is frequently mutating and rendering infective. Consequently, vaccination is the most effective approach in dealing with pneumococcal antimicrobial resistance (AMR). Unfortunately, the current pneumococcal polysaccharide and conjugate vaccines have a narrow serotype coverage. Therefore, the current need for vaccines with a broader serotype coverage cannot be overstated. Pneumococcal Surface Protein A and C are potential vaccine candidate antigens present in over 90% of the strains from clinical isolates as well as laboratory non-encapsulated strains. Pneumococcal Surface Protein A is an active virulent factor that pneumococci use to evade complement-mediated host immune responses and has been shown to elicit immune responses against pneumococcal infections. This review explores the potential utilization of Pneumococcal Surface Protein A to immunize against S. pneumoniae.

POSA198 Clinical and Economic Burden Attributable to Serotypes Included in Current and Future Pneumococcal Conjugate Vaccines in Argentinean Children Under Five Years of Age

After the 13-valent pneumococcal conjugate vaccine (PCV13) introduction into the National Immunization Program in Argentina for children in 2012, a significant reduction of pneumococcal disease was observed. PCVs in development, 15-valent (PCV15) and 20-valent (PCV20), are expected to expand pneumococcal disease coverage and address more pneumococcal disease burden due to inclusion of additional serotypes. Our objective was to estimate the annual clinical and economic burden caused by the serotypes included in currently licensed and investigational PCVs among Argentinean children under five years. A decision analytic model was used to calculate the burden of disease caused by serotypes contained in four PCVs. Epidemiologic, clinical, and cost data were estimated from published sources for children under five based on 2021 population figures. Invasive pneumococcal disease (IPD) serotype distribution by PCV formulation was derived from SIREVA II and used to extrapolate outcomes. Clinical outcomes included annual cases of IPD, inpatient and outpatient pneumonia, and acute otitis media (AOM), as well as deaths associated with IPD and outpatient pneumonia. Economic outcomes included direct costs by disease state and by each payer subsector. Based on reported serotype coverage, PCV20 is estimated to cover 55% of current pneumococcal disease, with 10-valent (PCV10), PCV13, and PCV15 covering 19%, 36% and 40%, respectively. Based on our assumptions, PCV20 serotypes caused more disease compared to other PCVs, causing a total of 352,973 annual cases. Of these, IPD represented an estimated 0.05%. Total direct attributable annual subsector costs were 29.1 million USD for private, 26.9 million USD for social security, and 22.3 million USD for public. Investigational PCVs that offer the broader serotype coverage will continue to protect infants against serotypes contained in current vaccines. PCV20 has the potential to deliver additional public health impact and economic value across all subsectors in Argentina.

Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection.

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged ≥65 years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2–3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18–22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

If Not Now, When? Nonserotype Pneumococcal Protein Vaccines.

The sudden emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have greatly accelerated the adoption of novel vaccine strategies, which otherwise would have likely languished for years. In this light, vaccines for certain other pathogens could certainly benefit from reconsideration. One such pathogen is Streptococcus pneumoniae (pneumococcus), an encapsulated bacterium that can express >100 antigenically distinct serotypes. Current pneumococcal vaccines are based exclusively on capsular polysaccharide—either purified alone or conjugated to protein. Since the introduction of conjugate vaccines, the valence of pneumococcal vaccines has steadily increased, as has the associated complexity and cost of production. There are many pneumococcal proteins invariantly expressed across all serotypes, which have been shown to induce robust immune responses in animal models. These proteins could be readily produced using recombinant DNA technology or by mRNA technology currently used in SARS-CoV-2 vaccines. A door may be opening to new opportunities in affordable and broadly protective vaccines.