This phase 3 trial compared immunogenicity and safety of 2-dose versus 3-dose PF-06425090 Clostridioides difficile vaccine regimens in ≥50-year-olds (N = 1994) at increased C difficile infection risk. Because C difficile toxin-A but not C difficile toxin-B immunogenicity noninferiority criteria were satisfied, the overall primary noninferiority objective was not met. Both regimens demonstrated similar safety profiles.

Streptococcus pneumoniae is an important cause of pneumonia in older adults, however, serotyping and indirect impact information from low and middle-income countries is lacking. Mongolia has a childhood 13-valent pneumococcal conjugate vaccine (PCV13) program, but no adult pneumococcal vaccination program. We describe pneumococcal carriage rates, disease and serotype distribution among adults hospitalised with pneumonia, and explore changes over the COVID-19 pandemic period. Adults (≥ 18 years) hospitalised with clinical pneumonia were enrolled over 3 years (March 2019-February 2022) into a prospective pneumonia surveillance program. Nasopharyngeal swabs were tested to detect pneumococci using lytA qPCR and molecular serotyping by DNA microarray and metagenomics. Pneumococcal pneumonia was identified using serotype-specific urinary antigen detection and BinaxNOW® assays. Pneumococcal carriage and pneumonia prevalence were assessed over the COVID-19 period with log-binomial regression used to estimate prevalence and adjusted prevalence ratios (pre- versus early- and late-COVID-19 periods). Of 3,178 pneumonia cases, S. pneumoniae was identified in 12.1

BACKGROUND:To characterize Clostridioides difficile isolates identified during a prospective multi-hospital population-based study of C. difficile infection (CDI). METHODS:Between December 2018 and March 2020, inpatients ≥50 years of age with new-onset diarrhea in nine Tokyo hospitals were investigated for CDI. Stool specimens were screened by C. DIFF QUIK CHEK COMPLETE® and glutamate dehydrogenase (GDH) positive stools tested by Xpert® C. difficile/Epi PCR assay. PCR positive stools were tested by cytotoxicity neutralization assay to determine presence of functional toxin. GDH positive stools were also anaerobically cultured and whole genome sequences of C. difficile isolates were acquired. RESULTS:Toxigenic C. difficile were isolated from 64 patients with CDI; 22 were RT018/356, 9 were RT369, 4 each were RT106 and RT002, 15 were other RTs, and 10 had an unknown RT. Four isolates were positive for binary toxin: one isolate each of RT027, RT078/126, RT080, and one unknown. In terms of the pathogenicity locus profile, 55 were tcdA+/tcdB+ and 9 were tcdA-/tcdB+. In terms of ST, 23 were ST17, nine were ST81, 31 were other STs, and one had a novel ST. CONCLUSIONS:Consistent with prior studies, C. difficile isolates from patients with CDI represented diverse ribotypes with approximately one third of isolates RT018/356. Of note, one isolate each of RT027 and RT078/126 were identified, indicating these hypervirulent strains are present in hospitals in Japan. Public health interventions are needed to reduce the CDI burden in Japan.

Background Serotype-specific urinary antigen detection (UAD) assay results can be used to estimate the serotype contribution among adults with pneumococcal community-acquired pneumonia (CAP) and to guide recommendations regarding higher-valency pneumococcal conjugate vaccines (PCVs).Methods Adults aged >= 18 years hospitalized with radiographic evidence of CAP were prospectively enrolled in 4 US cities from November 2019 to December 2020, overlapping the coronavirus disease 2019 (COVID-19) pandemic. Data were collected by patient interview and medical chart review. Streptococcus pneumoniae was isolated from standard-of-care respiratory samples and blood; urine collected per-protocol was tested by S pneumoniae BinaxNOW and UAD assays. The proportions of adults with radiologically confirmed CAP (RAD+ CAP) testing positive for S pneumoniae and for serotypes contained in PCV13, PCV15, and PCV20 were calculated.Results Among 3098 adults enrolled, 2105 (67.9%) had RAD+ CAP. Of these, 44.3% were >= 65 years of age, and most had a chronic medical condition (46.0%) or were immunocompromised (38.5%). Streptococcus pneumoniae was detected by any method in 214 (10.2%) RAD+ CAP participants, including 63 (3.0%) with serotypes covered by PCV13, 81 (3.9%) by PCV15, and 119 (5.7%) by PCV20. Streptococcus pneumoniae and PCV serotype positivity were higher before the pandemic (November 2019-April 2020) compared to during the COVID-19 pandemic (May 2020-December 2020).Conclusions Our study demonstrated that despite the COVID-19 pandemic, PCV serotype pneumococcus continued to cause an important proportion of adult CAP in the US. These data are useful for informing PCV recommendations and for establishing an epidemiologic baseline to assess the impact of such recommendations. The contribution of Streptococcus pneumoniae serotypes detected by serotype-specific urinary antigen detection assays among adults hospitalized with community-acquired pneumonia can inform vaccine policy on higher-valency pneumococcal conjugate vaccine recommendations among US adults.

Urinary antigen detection (UAD) assays can address diagnostic challenges with culture-based identification of S. pneumoniae. We aimed to evaluate the utility of Pfizer’s UAD1 and UAD2 assays for pneumococcal serotype surveillance in children with community acquired pneumonia (CAP) or upper respiratory tract infections (URI). From March 2021–December 2023, children 3 months to 5 years who presented to the Children’s Hospital Colorado Emergency Department with respiratory symptoms were enrolled as CAP or URI; healthy children served as controls. Nasal swabs were tested for pneumococcus by PCR. UAD assays identified pneumococcal serotypes from urine. Groups were compared using descriptive statistics. We enrolled 407 controls, 202 with URI, and 280 with CAP. Positivity thresholds were set for all UAD serotypes. Pneumococcal nasal swab positivity was 23

Background. Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention. Methods. This phase 3 observer-blinded study randomized (1:1) >= 50-year-olds at increased CDI risk (N = 17 535) to receive 3 PF-06425090 or placebo doses (0, 1, and 6 months). Primary end points were first CDI episode (>= 3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) >= 14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed. Results. The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode >= 14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], -38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode >= 14 days PD2 [VE = 28.6% (96.4% CI, -28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P =.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE = 100%; 95% CI, 59.6% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups. Conclusions. Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. Clinical Trials Registration. NCT03090191.

INTRODUCTION:Pneumococcus remains a major cause of adult lower respiratory tract infections (LRTI). Few data exist on the relative contribution of serotypes included in pneumococcal vaccines to community-acquired pneumonia (CAP) and non-pneumonic (NP) LRTI. We measured the burden of all and vaccine-serotype pneumococcal respiratory infection following SARS-CoV-2 emergence to inform evidence-based vaccination policy. METHODS:A prospective cohort study at two Bristol hospitals (UK) including all adults age ≥ 18-years hospitalised with acute lower respiratory tract disease (aLRTD) from Nov2021-Nov2022. LRTI patients were classified as: a) radiographically-confirmed CAP (CAP+/RAD+), b) clinically-diagnosed CAP without radiological confirmation (CAP+/RAD-), or c) NP-LRTI. Pneumococcus was identified by blood culture, BinaxNOW™and serotype-specific urine antigen detection assays (UAD). RESULTS:Of 12,083 aLRTD admissions, 10,026 had LRTI and 2,445 provided urine: 1,097 CAP + RAD+; 207 CAP + RAD-; and 1,141 NP-LRTI. Median age was 71.1y (IQR57.9-80.2) and Charlson comorbidity index = 4 (IQR2-5); 2.7 % of patients required intensive care, and 4.4 % died within 30-days of hospitalisation. Pneumococcus was detected in 280/2445 (11.5 %) participants. Among adults aged ≥ 65y and 18-64y, 12.9 % (198/1534) and 9.0 % (82/911), respectively, tested pneumococcus positive. We identified pneumococcus in 165/1097 (15.0 %) CAP + RAD+, 23/207 (11.1 %) CAP + RAD-, and 92/1141 (8.1 %) NP-LRTI cases. Of the 280 pneumococcal cases, 102 (36.4 %) were due to serotypes included in PCV13 + 6C, 115 (41.7 %) in PCV15 + 6C, 210 (75.0 %) in PCV20 + 6C/15C and 228 (81.4 %) in PPV23 + 15C. The most frequently identified serotypes were 8 (n = 78; 27.9 % of all pneumococcus), 7F (n = 25; 8.9 %), and 3 (n = 24; 8.6 %). DISCUSSION:Among adults hospitalised with respiratory infection, pneumococcus is an important pathogen across all subgroups, including CAP+/RAD- and NP-LRTI. Despite 20-years of PPV23 use in adults ≥ 65-years and herd protection due to 17-years of PCV use in infants, vaccine-serotype pneumococcal disease still causes a significant proportion of LRTI adult hospitalizations. Direct adult vaccination with high-valency PCVs may reduce pneumococcal disease burden.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia (CAP) in Japan. Here, we report the serotype distribution and antimicrobial susceptibility of cultured pneumococcal isolates from Japanese adults aged ≥18 years with CAP. This was a prospective, population-based, active surveillance study conducted in Goto City, Japan from December 2015 to November 2020. Pneumococcal isolates from sterile sites (blood and pleural fluid) and non-sterile sites (sputum and bronchoalveolar lavage) were cultured as part of the standard of care. S. pneumoniae were serotyped using the Quellung reaction. Antimicrobial susceptibility was tested using microdilution and interpreted according to the Clinical and Laboratory Standards Institute criteria. Isolates resistant to erythromycin were phenotyped using the triple-risk test and genotyped by polymerase chain reaction. A total of 156 pneumococcal isolates were collected (138 from sputum, 15 from blood, and 3 from bronchoalveolar lavage) from 1992 patients. Of these, 142 were non-duplicate isolates from unique patients and were included in the analyses. Serotypes contained within the 13-valent pneumococcal conjugate vaccine (PCV13) (including 6C), PCV15 (including 6C), and PCV20 (including 6C and 15C) were detected in 39 (27%), 45 (32%), and 80 (56%) of 142 isolates, respectively. The most common serotypes were 35B (12%), 11A (11%), and 3 (11%). Multidrug resistance (MDR) was detected in 96/142 (68%) isolates. Of the 96 MDR isolates, 31, 32, and 59% were PCV13, PCV15, and PCV20 serotypes, respectively; the most common MDR serotypes were 35B (16%), 6C, 10A, and 15A (9% each), and 3 and 11A (8% each). A total of 119 isolates were resistant to macrolides; 41 (35%) had an M phenotype, 53 (45%) had an iMcLS phenotype, and 25 (21%) had a cMLS phenotype. In conclusion, pneumococcal serotypes 35B, 11A and 3 were most frequently associated with pneumonia and antimicrobial resistance was common among pneumococcal isolates from adults with CAP in Goto City, Japan. Implementing higher-valency PCVs May help reduce vaccine-type CAP among Japanese adults.

BACKGROUND:This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post-dose 3. METHODS:One year post-dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively). RESULTS:In participants previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months post-dose 3 (36 months after placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased post-dose 4 (12 months post-dose 3) and persisted to 36 months post-dose 4. Thirty days post-dose 4, all participants had toxin A and 86.5% to 100% had toxin B titers at or above prespecified thresholds. Local reactions were more frequent in vaccine recipients. Systemic and adverse event frequencies were similar across groups. CONCLUSIONS:C difficile vaccine immune responses persisted 48 months post-dose 3. Dose 4 was immunogenic and well tolerated, supporting continued development. Clinical Trials Registration. ClinicalTrials.gov NCT02561195.

BACKGROUND:The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend pneumococcal disease protection beyond 13-valent PCV (PCV13). METHODS:This phase 3, double-blind study conducted in the United States/Puerto Rico evaluated PCV20 safety and immunogenicity. Healthy infants were randomized to receive a 4-dose series of PCV20 or PCV13 at 2, 4, 6 and 12-15 months old. Objectives included demonstrating noninferiority (NI) of PCV20 to PCV13 immunoglobulin G (IgG) geometric mean concentrations after doses 3 and 4 and percentages of participants with predefined IgG concentrations after dose 3, with 7 additional PCV20 serotypes compared with the lowest result among vaccine serotypes in the PCV13 group. Safety assessments included local reactions, systemic events, adverse events, serious adverse events and newly diagnosed chronic medical conditions. RESULTS:Overall, 1991 participants were vaccinated (PCV20, n = 1001; PCV13, n = 990). For IgG geometric mean concentrations 1 month after both doses 3 and 4, all 20 serotypes met NI criteria (geometric mean ratio lower 2-sided 95% confidence interval > 0.5). For percentages of participants with predefined IgG concentrations after dose 3, NI (percentage differences lower 2-sided 95% confidence interval > -10%) was met for 8/13 matched serotypes and 6/7 additional serotypes; 4 serotypes missed the statistical NI criterion by small margins. PCV20 also elicited functional and boosting responses to all 20 serotypes. The safety profile of PCV20 was similar to PCV13. CONCLUSION:A 4-dose series of PVC20 was well tolerated and elicited robust serotype-specific immune responses expected to help protect infants and young children against pneumococcal disease due to the 20 vaccine serotypes. Clinical trial registration: NCT04382326.

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

Background: A toxoid-based Clostridioides difficile vaccine is currently in development. Here, we report lot-to-lot consistency, immunogenicity, safety, and tolerability of 3 C difficile vaccine doses in healthy older adults. Methods: This phase 3, placebo-controlled study randomized (1:1:1:1) healthy adults 65 to 85 years of age to 1 of 3 C difficile vaccine lots or placebo. Participants received C difficile vaccine (200 mu g total toxoid) or placebo (Months 0, 1, 6). The primary immunogenicity objective was lot-to-lot consistency (2-sided 95 % CIs within 0.5 and 2 for comparisons of geometric mean concentration [GMC] ratios) for toxins A- and B-specific neutralizing antibody levels 1 month after Dose 3. Safety outcomes included local reactions and systemic events <= 7 days after vaccination, adverse events (AEs), and serious AEs (SAEs). Results: Of 1317 enrolled participants, 1218 completed the study. C difficile vaccine immunogenicity was consistent across lots, with neutralizing antibody responses 1 month after Dose 3 for both toxin A (GMC [95 % CI]: lot 1, 878.8 [786.3, 982.2]; lot 2, 873.0 [779.2, 978.1]; lot 3, 872.9 [782.6, 973.5]) and toxin B (lot 1, 5823.9 [5041.0, 6728.4]; lot 2, 5462.8 [4733.4, 6304.7]; lot 3, 5426.0 [4724.4, 6231.8]). Two-sided 95 % CIs for GMC ratios were within 0.5 and 2 for toxins A and B, indicating lot-to-lot consistency was achieved. C difficile vaccine was well tolerated, with similar rates of local reactions and systemic events among vaccine lots. AE and SAE rates were similar across C difficile vaccine (36.5 % and 4.5 %, respectively) and placebo (35.3 % and 6 %). Conclusions: Three doses (Months 0,1,6) of toxoid-based C difficile vaccine induced robust neutralizing antibody responses and were well tolerated in healthy participants 65 to 85 years of age. Lot-to-lot consistency was excellent, indicating the manufacturing process for this C difficile vaccine formulation was well controlled. Clinical trial registration: ClinicalTrials.gov identifier: NCT03579459.

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

Abstract Background Invasive pneumococcal disease (IPD) serotype distribution has been used to infer the serotype distribution of pneumococcal community acquired pneumonia (pCAP) in countries where only IPD data exist. However, serotype distribution of IPD and pCAP may differ. We sought to identify differences in contribution of serotypes causing pCAP versus IPD. Methods Eligible countries had serotype data available from adults for both IPD (determined by standard serotyping methods of cultured isolates) and pCAP (determined by serotype-specific urinary antigen detection (UAD) assays or culture for at least three years following PCV13 introduction into the pediatric national immunization program (NIP). Analyses were restricted to serotypes included in UAD assays. We further restricted analysis to serotypes not in PCV13 but detected by UAD assays (serotypes 2, 8, 9N, 10A, 11A, 12F, 15B/C, 17F, 20, 22F, and 33F), because PCV13 introduction into the NIPs has led to vaccine serotype disease reduction. The total positive of these serotypes was the denominator in the serotype-specific proportion calculations for both IPD and pCAP Results We included seven countries. IPD serotype as well as pCAP distribution varied substantially across countries, while within countries, IPD and pCAP serotype distribution varied modestly (Figure1, Table 1) For the three most common pCAP serotypes across the seven countries, the absolute differences in the percent due to pCAP across countries were 19% (serotype 8), 10% (serotype 22F) and 10% (serotype 11A). For the same three serotypes, respectively, the absolute differences in the percent due to IPD across countries were 47%, 18%, and 17%. For these same three serotypes, the absolute differences in the percent due to pCAP vs, IPD within a country ranged from 1% to 14%, 1% to 6%, and 2% to 11%. Conclusion pCAP and IPD serotype distribution were relatively aligned within countries. By contrast IPD and pCAP serotype distribution varied substantially across countries. Consequently, while the most accurate data for country-specific pneumococcal vaccine decision-making will come from combined IPD and CAP studies, countries without CAP data should rely on local IPD serotype distribution rather than CAP data from other countries. Disclosures Kevin Apodaca, MPH, Pfizer Inc.: Stocks/Bonds Lindsay Grant, PhD, MPH, Pfizer Inc.: Stocks/Bonds Qi Yan, PhD, MS, Pfizer Inc: Stocks/Bonds Christian Theilacker, MD, DTM&H, Pfizer Inc: Stocks/Bonds Mohammad Ali, PhD, Pfizer Inc: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Stocks/Bonds Bradford D. Gessner, M.D., M.P.H., Pfizer: I am an employee of Pfizer|Pfizer: Stocks/Bonds Luis Jodar, PhD, Pfizer Inc: Stocks/Bonds

Abstract Background Diagnosis of Lyme Disease has relied on measuring the serological response to Borrelia sp. Over the years the rigor of serological diagnosis has evolved to meet the needs of the clinic and vaccine manufacturers, where the latter require especially sensitive and specific tests to measure efficacy. Likewise, current US guidelines recommend a two-tier testing approach to diagnose Lyme Disease. Among a constellation of commercially available in vitro diagnostics, two highly sensitive immunoassays with Borrelia sp. antigenic diversity were characterized for utility as a custom Modified Two-Tier Testing (MTTT) algorithm. This custom algorithm consists of a first tier assay from Bio-Rad and a second tier assay from Zeus Scientific, and was developed to capture cases of Lyme Disease. Methods The BioPlex 2200 Lyme Total assay from BioRad and VlsE1/pepC10 IgG/IgM ELISA from Zeus Scientific were evaluated as the first and second tier assays in the custom MTTT, respectively. The MTTT was clinically assessed for diagnostic accuracy and compared to the highly characterized CDC Pre-Marketing Panel, which is composed of samples from US donors diagnosed with Lyme Disease, “look-alike” diseases or healthy individuals. Other clinically relevant sample populations were benchmarked off the predicate FDA-approved MTTT, also from Zeus Scientific. Results The custom MTTT, described here, was more clinically specific than either test alone and was more clinically sensitive than the only other FDA-approved MTTT. When matched against the FDA-approved predicate method, sensitivity and specificity was 100%. The custom MTTT also detected fewer “look-alike” disease samples than either test alone, or the FDA-approved MTTT. Furthermore, detection of early Lyme Disease in the CDC Pre-Marketing panel was 80% sensitive. In addition, the custom MTTT identified Lyme disease in 98.6% of Lyme Disease samples collected from samples that originated in Europe. Conclusion The clinically validated custom MTTT method, described here, has utility as a Lyme Disease diagnostic and is a highly specific tool for assessing efficacy of Lyme Disease vaccines currently in development. Disclosures Michelle A. Gaylord, PhD, Pfizer Inc.: Stocks/Bonds Danielle Baranova, PhD, Pfizer Inc: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Warren Vincent. Kalina, PhD, Pfizer: Stocks/Bonds

Implementation of conjugate vaccine technology revolutionized the ability to effectively elicit long-lasting immune responses to bacterial capsular polysaccharides. Although expansion of conjugate vaccine serotype coverage is designed to target residual disease burden to pneumococcal serotypes not contained in earlier vaccine versions, details of polysaccharide Ag structure, heterogeneity, and epitope structure components contributing to vaccine-mediated immunity are not always clear. Analysis of Streptococcus pneumoniae serotype 12F polysaccharide by two-dimensional nuclear magnetic resonance spectroscopy and mass spectrometry revealed a partial substitution of N-acetyl-galactosamine by the keto sugar 2-acetamido-2,6-dideoxy-xylo-hexos-4-ulose (Sug) in up to 25% of the repeat units. This substitution was not described in previous published structures for 12F. Screening a series of contemporary 12F strains isolated from humans (n = 17) identified Sug incorporation at varying levels in all strains examined. Thus, partial Sug substitution in S. pneumoniae serotype 12F may have always been present but is now detectable by state-of-the-art analytical techniques. During the steps of conjugation, the serotype 12F Sug epitope is modified by reduction, and both polysaccharide PPSV23 and conjugate PCV20 vaccines contain 12F Ags with little to no Sug epitope. Both PCV20 and PPSV23 vaccines were evaluated for protection against circulating 12F strains with varying amounts of Sug in their repeat unit based on an opsonophagocytic killing assay involving HL-60 cells and rabbit complement. Both vaccines elicited human-derived neutralizing Abs against serotype 12F, independent of Sug level between ∼2 and 25 mol%. These findings suggest that the newly identified serotype 12F Sug epitope is likely not an essential epitope for vaccine-elicited protection.

Although Clostridioides difficile infection (CDI) incidence is high in the United States, standard-of-care (SOC) stool collection and testing practices might result in incidence overestimation or underestimation. We conducted diarrhea surveillance among inpatients >50 years of age in Louisville, Kentucky, USA, during October 14, 2019-October 13, 2020; concurrent SOC stool collection and CDI testing occurred independently. A study CDI case was nucleic acid amplification test‒/cytotoxicity neutralization assay‒positive or nucleic acid amplification test‒positive stool in a patient with pseudomembranous colitis. Study incidence was adjusted for hospitalization share and specimen collection rate and, in a sensitivity analysis, for diarrhea cases without study testing. SOC hospitalized CDI incidence was 121/100,000 population/year; study incidence was 154/100,000 population/year and, in sensitivity analysis, 202/100,000 population/year. Of 75 SOC CDI cases, 12 (16.0%) were not study diagnosed; of 109 study CDI cases, 44 (40.4%) were not SOC diagnosed. CDI incidence estimates based on SOC CDI testing are probably underestimated.

Background Few studies have measured the burden of community-acquired pneumonia (CAP) and pneumococcal vaccine-type CAP in Japan after the introduction of the 23-valent pneumococcal polysaccharide vaccine into the adult national immunization program (NIP) for individuals ≥ 65 years of age in 2014. In this study, we estimated the incidences of CAP and Streptococcus pneumoniae CAP among Japanese adults between 2015 and 2020. Research Question What are the incidences of CAP and S pneumoniae CAP among Japanese adults? What are the common pneumococcal serotypes detected in patients with S pneumoniae CAP? Study Design and Methods This prospective, population-based, multicenter, active surveillance study enrolled adults ≥ 18 years of age with clinically and radiologically confirmed CAP in Goto City, Japan. S pneumoniae was detected using standard-of-care blood and sputum cultures, BinaxNOW, and serotype-specific urinary antigen detection assays. Results A total of 2,103 patients with CAP were enrolled; 84% were ≥ 65 years of age and 6.7% died during the study. The annual CAP, S pneumoniae CAP, 13-valent pneumococcal conjugate vaccine (PCV13) serotype CAP, and 20-valent pneumococcal conjugate vaccine (PCV20) serotype CAP incidences per 100,000 population were 1,280, 227, 63, and 110, respectively. S pneumoniae was detected in 17.8% of all patients with CAP by any detection method, with 4.9%, 5.5%, and 8.6% of cases of CAP resulting from PCV13, 15-valent pneumococcal conjugate vaccine, and PCV20 serotypes, respectively. Applying Goto's incidence and case fatality rate to the Japanese population, assuming PCV20 has the same vaccine efficacy and duration of protection as PCV13 and if licensed in Japan for the prevention of CAP, the inclusion of PCV20 in the NIP for adults ≥ 65 years of age could prevent 29,036 cases of CAP and 2,275 CAP-related deaths per year. Interpretation Given the substantial burden of preventable pneumococcal disease, introduction of pneumococcal conjugate vaccines in Japanese adults may be of merit.

OBJECTIVES:Clostridioides difficile infection (CDI) burden is not well-characterized in Japan. Therefore, we conducted a population-based, hospitalized CDI incidence study, compared the results with standard-of-care (SOC) CDI testing, and generalized the results for nationwide incidence estimates. METHODS:Surveillance identified inpatients ≥50 years-of-age with diarrhea in nine Tokyo hospitals from December 17, 2018-March 30, 2020. A CDI case was defined as a patient with a PCR-positive/cell cytotoxicity neutralization assay (CCNA)-positive stool or a PCR-positive stool and pseudomembranous colitis (PMC). Incidence estimates were adjusted for the hospitalization share of participating hospitals and, in the sensitivity analysis, for missing CDI test results. SOC specimen collection and CDI testing occurred independently. RESULTS:Surveillance during 318 840 patient-days identified 4633 inpatients with diarrhea. Sixty-three CDI cases were identified; 11 (17·5%) had PMC, eight (12·7%) recurrent CDI, and nine (14·3%) died. The hospitalized CDI incidence was 97/100 000 population per year (PPY) in persons ≥50 years-of-age and, in the sensitivity analysis, 324/100 000 PPY. The incidence was 170 and 481/100 000 PPY in persons ≥65 and ≥85 years-of-age, respectively; these estimates increased to 569 and 1609/100 000 PPY in the sensitivity analysis, respectively. There were 12 primary SOC CDI cases in persons ≥50 years-of-age (18/100 000 PPY). CONCLUSIONS:The CDI incidence was high in older adults, with severe clinical consequences. SOC specimen collection and testing under-estimated CDI burden. There are >57 000 hospitalized CDI cases per year in Japan in persons ≥50 years-of-age. Public health interventions are needed to reduce the CDI burden in Japan.