Background: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. Methods: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. Results: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48–0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. Conclusions: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Objectives: Safety and immunogenicity evaluation of a 4-dose series with 20-valent pneumococcal conjugate vaccine (PCV20). Methods: This phase 3, double-blind study randomized healthy Japanese infants to receive 4 doses (3 infant doses, 1 toddler dose) of PCV20 by subcutaneous (SC) or intramuscular (IM) injection or 13-valent PCV (PCV13) SC. A primary immunogenicity objective was to demonstrate noninferiority of PCV20 SC to PCV13 SC for percentages of participants meeting predefined serotype-specific immunoglobulin G concentrations 1 month after Dose 3. The 7 additional PCV20 serotypes were compared with the lowest vaccine serotype result in the PCV13 group. Safety and tolerability were assessed as the primary safety objective. Results: Overall, 668 participants were randomized (PCV20 SC, n = 226; PCV13 SC, n = 224; PCV20 IM, n = 218). The primary noninferiority objective for PCV20 SC to PCV13 SC was met for 11/13 matched and 5/7 additional serotypes. Additional data showed PCV20 SC and IM elicited robust functional opsonophagocytic activity and boosting responses to all 20 vaccine serotypes. PCV20 had a similar safety/tolerability profile to PCV13, although local reactions were less frequent with PCV20 IM. Conclusions: A 4-dose series of PCV20 SC or IM elicited immune responses expected to be protective against all 20 serotypes in Japanese infants. NCT04530838

BACKGROUND AND OBJECTIVES:The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection for pneumococcal disease. It contains all 13-valent pneumococcal conjugate vaccine (PCV13) components plus conjugates for 7 additional serotypes. Our primary objective with this study was to evaluate PCV20 tolerability and safety. METHODS:In this phase 3, multi-country, double-blind study, healthy infants born at ≥34 weeks' gestation were randomly assigned 2:1 to receive PCV20 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety assessments included local reactions and systemic events within 7 days after each vaccination, adverse events (AEs) from dose 1 to 1 month after dose 3 and from dose 4 to 1 month after dose 4, and serious AEs and newly diagnosed chronic medical conditions from dose 1 through 6 months after the last dose. RESULTS:Participants received PCV20 (N = 1000) or PCV13 (N = 504); 91.7% received all 4 doses. The frequencies of local reactions and systemic events were generally similar in PCV20 and PCV13 groups, with most reported as mild or moderate. The most common local reaction was injection site pain (PCV20, 24.7% to 40.5%; PCV13, 26.8% to 42.0%); irritability was the most common systemic event (PCV20, 54.8% to 68.2%; PCV13, 54.7% to 68.5%). AE frequencies were similar in both groups. No serious AEs were related to study vaccines. Few newly diagnosed chronic medical conditions were reported (2.8% in both groups). PCV20 was safe across multiple countries, in late preterm infants, and when administered with other vaccines. CONCLUSIONS:A 4-dose series of PCV20 had a tolerability and safety profile similar to that of PCV13.

Background: Pneumococcal infections are associated with high disease burden in older individuals in Japan, South Korea, and Taiwan. The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to extend protection beyond earlier pneumococcal vaccines. Methods: This phase 3 randomized, double-blind study investigated the safety and immunogenicity of PCV20 in participants >= 60 years of age from Japan, South Korea, and Taiwan. Participants were randomized to receive PCV20 or 13-valent pneumococcal conjugate vaccine (PCV13). One month after vaccination, PCV20 recipients received a saline injection and PCV13 recipients received 23-valent polysaccharide vaccine (PPSV23). Primary immunogenicity objectives were to demonstrate noninferiority of PCV20 to PCV13 (13 matched serotypes) or PPSV23 (7 additional serotypes) for serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1 month after vaccination with PCV20, PCV13, or PPSV23. Noninferiority for each serotype was declared if the lower bound of the 2-sided 95% CI for OPA geometric mean ratio (GMR) was > 0.5. Safety endpoints included local reactions, systemic events, adverse events (AEs), and serious AEs. Results: Overall, 1421 participants were vaccinated (median age [range]: 65 [60-85] years). PCV20 was noninferior to PCV13 for all 13 matched serotypes and to PPSV23 for 6 of 7 additional serotypes. Although statistical noninferiority was missed for serotype 8 (lower bound of the 2-sided 95% CI for OPA GMR = 0.5, thus not meeting the statistical noninferiority criterion of > 0.5), secondary immunogenicity endpoints for serotype 8 were supportive of a robust immune response. The incidence of AEs and the frequency and severity of local reactions and systemic events were generally similar after PCV20 and PCV13. No safety concerns were identified. Conclusion: PCV20 generated robust immune responses to all vaccine serotypes in older adults in Japan, South Korea, and Taiwan. The safety and tolerability profile was similar to PCV13. PCV20 is expected to help protect against all 20 vaccine serotypes. NCT04875533.

BACKGROUND:A 20-valent pneumococcal conjugate vaccine (PCV20), containing 13-valent PCV (PCV13) components and 7 additional polysaccharide conjugates, was developed to extend protection for pneumococcal disease. This phase 3 study assessed the safety and immunogenicity of PCV20 in children. METHODS:In this single-arm study, children (≥15 months-<18 years of age) received 1 dose of PCV20. Children <5 years of age had ≥3 prior doses of PCV13; children ≥5 years were recruited regardless of previous PCV receipt. Serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers were measured before and 1 month after PCV20. Local reactions and systemic events, adverse events (AEs), serious AEs, and newly diagnosed chronic medical conditions were collected. RESULTS:Of 839 enrolled participants, 831 (>99%) were vaccinated, and 819 (>97%) completed all study visits. Local reactions and systemic events were mostly mild to moderate in severity. No serious AEs were considered PCV20-related. IgG geometric mean fold rises (GMFRs) from before to 1 month after PCV20 ranged from 27.9-1847.7 (7 additional serotypes) and 2.9-44.9 (PCV13 serotypes) in children <5 years of age, and 10.5-187.7 (7 additional serotypes) and 4.3-127.9 (PCV13 serotypes) in children ≥5 years old. OPA GMFRs from before to 1 month after PCV20 ranged from 12.4-983.6 to 2.8-52.9 in children <5 years of age and from 11.5-499.0 to 5.3-147.9 in children ≥5 years of age. CONCLUSIONS:Among children ≥15 months through <18 years of age, PCV20 was well tolerated and induced robust responses to all 20 serotypes, supporting the use of PCV20 in children.

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: Older adults are at increased risk of adverse outcomes from pneumococcal disease and COVID-19. Vaccination is an established strategy for preventing both illnesses. This study evaluated the safety and immunogenicity of coadministration of the 20-valent pneumococcal conjugate vaccine (PCV20) and a booster (third dose) of BNT162b2 COVID-19 vaccine.Methods: This phase 3, randomized, double-blind, multicentre study included 570 participants aged & GE;65 years randomized 1:1:1 to PCV20 and BNT162b2 coadministered, or PCV20 or BNT162b2 only (administered with saline for blinding). Primary safety endpoints included local reactions, systemic events, adverse events (AEs) and serious AEs (SAEs). Secondary objectives were immunogenicity of PCV20 and BNT162b2 when administered together or separately. Results: Coadministration of PCV20 and BNT162b2 was well tolerated. Local reactions and systemic events were generally mild-moderate; injection-site pain and fatigue were the most frequent local and systemic events, respectively. AE and SAE rates were low and similar across groups. No AEs led to discon-tinuation; no SAEs were considered vaccination-related. Robust immune responses were observed, with opsonophagocytic activity geometric mean fold rises (GMFRs; from baseline to 1 month) of 2.5-24.5 and 2.3-30.6 across PCV20 serotypes in Coadministration and PCV20-only groups, respectively. GMFRs for full-length S-binding IgG of 35.5 and 39.0, and for neutralizing titres against SARS-CoV-2-wild type virus of 58.8 and 65.4, were observed in the Coadministration and BNT162b2-only groups, respectively.Conclusions: Safety and immunogenicity of coadministered PCV20 and BNT162b2 were similar to those of PCV20 or BNT162b2 administered alone, suggesting that the 2 vaccines may be coadministered. Trial Registration: ClinicalTrials.gov, NCT04887948. & COPY; 2023 Elsevier Ltd. All rights reserved.

Abstract Background The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection against pneumococcal disease. PCV20 contains conjugates for serotype 6A, which is also in 13-valent PCV (PCV13) and appears to have had a clinical impact on 6C disease, and the additional serotype 15B. An exploratory assessment of cross-reactive functional antibodies to serotypes 6C and 15C elicited by PCV20 in two phase 3 infant studies is described. Methods Two randomized phase 3 studies evaluated immunogenicity and safety of PCV20 relative to PCV13 in infants receiving a 4-dose series (3 infant doses and a toddler dose; NCT04382326) or a 3-dose series (2 infant doses and a toddler dose; NCT04546425). In each study, immunoglobulin G (IgG) concentrations and opsonophagocytic activity (OPA) titers to serotypes 6C and 15C were measured in a randomly selected subset of infants 1 month after the infant doses, and before and 1 month after the toddler dose. IgG geometric mean concentrations, OPA geometric mean titers (GMTs), and percentage of participants with predefined IgG concentrations, and OPA titers greater than or equal to the lower limit of quantitation were calculated with 95% confidence intervals. Results PCV20 elicited IgG and OPA responses to serotype 6C that were generally similar for most endpoints to PCV13 after the 3 infant and toddler doses in the 4-dose series study and after the toddler dose in the 3-dose series study. PCV20 also elicited both IgG and OPA responses to 15C after the infant and toddler doses that were well differentiated from the PCV13 group in both studies. After the toddler dose, OPA GMTs to serotype 6C in the PCV20 and PCV13 groups were 422 and 995, respectively, following a 3-dose series, and 824 and 1090 following a 4-dose series. OPA GMTs to serotype 15C were 67 and 38 and 117 and 38 at the same timepoint in the PCV20 and PCV13 groups, respectively. Conclusion PCV20 elicits cross-reactive IgG and cross-functional OPA responses to serotypes 6C and 15C. The responses to serotype 6C after PCV20 are generally similar to those of PCV13. The epidemiology of disease due to the vaccine-type and vaccine-related serotypes will be monitored after introduction of PCV20 into infant immunization programs. Funded by Pfizer Inc Disclosures Noor Tamimi, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Mary J. Kline, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Kimberly J. Center, M.D., Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Allison Thompson, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Gary Baugher, PharmD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jelena Drozd, MS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Ingrid L. Scully, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Peter Giardina, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds James Trammel, MS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Lanyu Lei, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Yahong Peng, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Daniel Scott, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Wendy Watson, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds

Abstract Background The 20-valent pneumococcal conjugate vaccine (PCV20), developed to expand protection against pneumococcal disease, is approved for adults in several countries and for pediatric use in the United States. Tolerability and safety data from PCV20 pediatric studies are described. Methods Five randomized studies in infants (1 Phase 2; 4 Phase 3) assessing the safety of PCV20 relative to 13-valent PCV (PCV13) receiving a 3- or 4-dose series (2 or 3 primary series doses and a toddler dose) were conducted in North America, Europe, South America, and Japan. Study vaccines were given intramuscularly in all studies except in Japan, where a subcutaneous (SQ) route was also evaluated. A single-arm Phase 3 study of 1 PCV20 dose was performed in US children 15 months to 17 years old; children < 5 years old had received ≥ 3 doses of PCV13. All studies assessed local reactions and systemic events within 7 days of vaccination. Adverse events (AEs) were collected through 1 month after the primary series (infant studies) and 1 month after the toddler or single vaccine dose. Serious AEs (SAEs) were collected throughout study participation. Results The safety population across 6 studies totaled 6654 participants; 3276 infants and 831 children received PCV20 and 2547 infants received PCV13. Overall, the most common local reaction was injection site pain, except in the infant study in Japan, where redness was most common, particularly in SQ groups. In the infant studies, the most common systemic events were irritability and drowsiness. The most common systemic events in older children were fatigue (≥ 2- to < 5-year-old age group) and muscle pain (≥ 5- to ≤ 17-year-old age group). Fever > 40°C was uncommon (PCV20, ≤ 0.5%; PCV13, ≤ 0.1% after any dose). AE and SAE rates were similar to the PCV13 group in the infant studies and low in the study in children. Events were consistent with illnesses and medical conditions that may occur in pediatric populations. Conclusion In 6 studies conducted globally, PCV20 was safe and well tolerated in infants and children through 17 years of age. The PCV20 tolerability and safety profile was similar to PCV13 controls in infant studies and consistent with PCV13 studies in children. FUNDING BY PFIZER INC Disclosures Laurence Flint, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Kathleen McElwee, MD, MDH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds G. Laissa Ouedraogo, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Noor Tamimi, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Mary J. Kline, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Kimberly J. Center, M.D, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Allison Thompson, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Richard de Solom, MBBS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Masako Yamaji, MS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds James Trammel, MS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Lanyu Lei, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Yahong Peng, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Daniel Scott, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Wendy Watson, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds

Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates from 7 non-13-valent (PCV13) serotypes was developed to potentially complement PCV13-mediated protection and expand serotype coverage. This study evaluated cPCV7 and PCV13 coadministered in separate limbs or separated in time in infants. This phase 2, multicenter, open-label study included 512 infants randomized 1:1:1 to receive cPCV7 coadministered with PCV13 at ages 2, 4, 6, and 12 months (cPCV7 Coadministered); cPCV7 given at ages 3, 5, 7, and 13 months, 3-5 weeks after PCV13 (cPCV7 Separated); or PCV13 at ages 2, 4, 6, and 12 months followed by a single supplemental dose of cPCV7 at 13 months (PCV13 Control). Safety evaluations included local reactions, systemic events, and adverse events. Serotype-specific immunoglobulin G concentrations and opsonophagocytic activity titers were assessed. The safety profile of cPCV7 was similar to that of PCV13. cPCV7 was well-tolerated in infants when coadministered with or given separately from PCV13. Robust and functional immune responses for all cPCV7 serotypes were observed in both cPCV7 groups. No immunologic interference was observed for either the cPCV7 or PCV13 serotypes with coadministration. A single cPCV7 dose induced immune responses in toddlers. These findings support potential coadministration of a complementary PCV to supplement protection provided by existing PCVs.Trial registration: ClinicalTrials.gov, NCT03550313.

Introduction: Older adults are at increased risk of adverse outcomes from pneumococcal disease and influenza infections. Vaccination is an established strategy for preventing both illnesses. This study eval-uated coadministration of 20-valent pneumococcal conjugate vaccine (PCV20) and an adjuvanted quadri-valent inactivated influenza vaccine (QIV).Methods: This phase 3, randomized, double-blind, multicenter study included 1796 US adults >= 65 years of age randomized 1:1 to receive either PCV20 and QIV followed 1 month later by saline (Coadministration group) or QIV and saline followed 1 month later by PCV20 (Separate Administration group). Primary immunogenicity objectives were to show noninferiority of PCV20 and QIV coadministra-tion compared with separate administration of either vaccine based on serotype-specific opsonophago-cytic activity (OPA) titers for PCV20 and strain-specific hemagglutination inhibition assay (HAI) titers for QIV. Safety endpoints included local reactions, systemic events, and adverse events (AEs).Results: Noninferiority for pneumococcal and influenza antibody responses (lower bound 95 % CI of the OPA and HAI geometric mean ratios of > 0.5 and > 0.67, respectively) was shown for the Coadministration group compared with the Separate Administration group for all 20 pneumococcal ser-otypes and all 4 influenza vaccine strains. Local reactions and systemic events were mostly mild or mod-erate in severity across groups; injection site pain was the most frequent local reaction, and fatigue was the most frequent systemic event. Mild and moderate fatigue were reported more frequently after PCV20 and QIV coadministration compared with separate administration (mild, 20.0 % vs 10.8 %-12.6 %; moder-ate, 12.3 % vs 8.4 %-9.6 %); this was not considered clinically significant. AE reporting rates were similar across groups, and no serious AEs were considered vaccination-related.Conclusions: Immune responses after coadministration of PCV20 and QIV were noninferior to separate administration of either vaccine. The PCV20 safety profile was similar when given together with or after QIV. These findings support PCV20 and QIV coadministration.Trial Registration: ClinicalTrials.gov, NCT04526574.(c) 2022 Published by Elsevier Ltd.

Abstract Background Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated. Methods This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50–59, and 18–49 years) at US and Swedish sites. Participants were randomized to receive 1 PCV20 or 13-valent PCV (PCV13) dose. After 1 month, participants aged ≥60 years also received 1 dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity geometric mean titers 1 month after PCV20 were compared with 13 matched serotypes after PCV13 and 7 additional serotypes after PPSV23 in participants aged ≥60 years; noninferiority was declared if the lower bound of the 2-sided 95% confidence interval for the opsonophagocytic activity geometric mean titer ratio (ratio of PCV20/saline to PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60–64-year-olds. Results The severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants aged ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups. Conclusions PCV20 was safe and well tolerated, with immunogenicity comparable to that of PCV13 or PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults. Clinical Trials Registration NCT03760146.

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 registrationNCT03760146, NCT03828617.

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

Expanding serotype coverage of pneumococcal conjugate vaccines (PCVs) to target prevailing disease-causing serotypes could further reduce disease burden. To address this need, 2 different PCVs have been investigated: a 20-valent PCV (PCV20; includes the 13 serotypes in the 13-valent PCV [PCV13] plus 7 additional serotypes [8, 10A, 11A, 12F, 15B, 22F, 33F]) and a complementary 7-valent PCV (cPCV7; contains only the 7 additional serotypes). This phase 1b, randomized, controlled, double-blind study evaluated PCV20 and cPCV7 safety and immunogenicity in healthy Japanese adults 18–49 years of age residing in the United States for ≤5 years. Participants (n = 104) were randomized equally to receive a single dose of PCV20, cPCV7, or PCV13. Immunogenicity was assessed at baseline and 1 month after vaccination using serotype-specific opsonophagocytic activity (OPA) titers and serotype-specific immunoglobulin G (IgG) concentrations. Prompted local reactions and systemic events; adverse events (AEs); and serious AEs and newly diagnosed chronic disease were assessed 14 days, through 1 month, and upto 6 months following vaccination, respectively. OPA immune responses were robust for all 20 serotypes in the PCV20 group and for the 7 serotypes in the cPCV7 group 1 month after vaccination. IgG immune response showed similar trends. Injection site pain and muscle pain were the most common local reaction and systemic event; the majority were mild or moderate in severity. Few AEs and no severe AEs, serious AEs, or safety-related withdrawals were reported. Taken together, administration of PCV20 or cPCV7 in Japanese adults was well tolerated and induced robust serotype-specific functional immune responses. NCT03642847.

Background: Two phase 1/phase 2 studies assessed 2 formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) in healthy adults 50-85 years of age. Methods: The QS-21 adjuvanted toxoid vaccine study randomized subjects 3:1 to 100 mu g QS-21-containing C difficile vaccine or placebo administered in a shortened-month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 mu g unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3 (Days 1, 8, 30). Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A- and B-specific neutralizing antibodies. Results: In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%-75.0% and 16.7%-50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen) and remained above baseline throughout follow-up. Conclusions: Both formulations demonstrated robust immunogenicity. Both studies stopped early due to grade 3 injection site redness postdose 2 of the day regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies. (C) 2021 Pfizer Inc. Published by Elsevier Ltd.

Abstract Background PCV20 contains the 13-valent pneumococcal conjugate vaccine (PCV13) components, and 7 additional conjugates (for serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F), extending pneumococcal serotype coverage. Key data from the pivotal Phase 3 evaluation of PCV20 in adults are presented. Methods Adults naïve to pneumococcal vaccination were enrolled into 3 age cohorts (≥60, 50–59, and 18–49 years of age). Participants ≥60 years received either PCV20 and saline 1 month later, or PCV13 and 23-valent pneumococcal polysaccharide (PPSV23) 1 month later (1:1 randomization, double blind). Participants 50–59 and 18–49 years received either a dose of PCV20 or PCV13 (3:1 randomization, double blind). Tolerability, safety and immunogenicity (opsonophagocytic activity [OPA] responses) were assessed. Results 3889 participants received vaccine. 1507 and 1490 participants ≥60 years received PCV20 or control respectively. All 20 vaccine serotypes induced robust responses and OPA geometric mean titers (GMTs) to all 13 matched serotypes were noninferior to PCV13. In addition, the OPA GMTs to 6 of the 7 additional serotypes 1 month after PCV20 were noninferior compared to the same serotypes in PPSV23. The OPA GMT of serotype 8 missed noninferiority by a very narrow margin (2-sided 95% lower bound of GMT ratio [20vPnC/PPSV23] was 0.49, with noninferiority criterion of >0.5); this is unlikely to be clinically significant given the high geometric mean fold rise of OPA titers after PCV20 (22-fold above baseline). GMTs after PCV20 in each of the younger age cohorts (18–49 years, 50–59 years) were noninferior to adults 60–64 years. The tolerability and safety profile of PCV20 was similar to PCV13. Conclusion Based on the robust immune responses and comparability to licensed pneumococcal vaccines, as well as bridging to the younger age group, these data support that PCV20 will be protective against pneumococcal disease due to the 20 serotypes in adults. Disclosures Charu Sabharwal, MD, MPH, Pfizer (Employee, Shareholder) Xia Xu, PhD, Pfizer (Employee, Shareholder) Vani Sundaraiyer, PhD, MS, Pfizer (Independent Contractor) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Lisa Moyer, BS, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)

Abstract Background Two formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) were assessed for safety and immunogenicity in randomized studies in healthy adults 50–85 years of age. Methods The Phase 1 study of QS-21 adjuvanted toxoid vaccine randomized subjects 3:1 to 100 μg QS-21-containing C difficile vaccine or placebo; 3 doses were given according to 2 different schedules: a shortened month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The Phase 2 toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 μg unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3. Three doses were given on a day (Days 1, 8, 30) regimen. Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A– and B–specific neutralizing antibodies. Results In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%–75.0% and 16.7%–50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen), and remained above baseline throughout follow-up. Conclusion Both formulations demonstrated robust immunogenicity. However, both studies stopped early due to grade 3 injection site redness postdose 2 of the day (Days 1, 8, 30) regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies. Disclosures Jody Lawrence, MD, Pfizer, Inc (Employee) Nicholas Kitchin, MD, Pfizer, Inc (Employee) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Charles Knirsch, MD, Pfizer (Employee) Chris Webber, MD, Pfizer Inc (Employee, Shareholder)

Abstract Background A 20-valent pneumococcal conjugate vaccine (PCV20) is being developed to extend protection against pneumococcal disease beyond that of the 13-valent pneumococcal vaccine (PCV13). This is the first safety and immunogenicity study of PCV20 in healthy infants. Methods This randomized, double-blind study enrolled and randomized (1:1) healthy infants ≥ 42 to ≤ 98 days of age to receive a 4-dose series of either PCV20 or PCV13 (control) at 2, 4, 6, and 12 months of age. Local reactions and systemic events were assessed for 7 days after each vaccination; adverse events (AEs) and serious AEs (SAEs) were collected throughout the study. PCV20 immune responses (serotype-specific immunoglobulin G [IgG] and opsonophagocytic activity [OPA]) were measured in sera 1 month after the third infant dose and the fourth dose at 12 months of age. Results There were 460 subjects enrolled, with 416 and 391 subjects receiving 3 and 4 doses, respectively. Local reactions and systemic events were predominantly mild to moderate in severity and similar among vaccine groups. There were no related SAEs or deaths reported. PCV20 elicited IgG responses 1 month after the third dose with boosting after a fourth dose. OPA responses were also observed. Conclusion PCV20 was well tolerated with a safety profile similar to PCV13. PCV20 elicited immune responses to all 20 vaccine serotypes. Disclosures Shelly Senders, MD, Pfizer (Grant/Research Support) Nicola P. Klein, MD, PhD, GSK group of companies (Research Grant or Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Protein Science (now SP) (Grant/Research Support)Sanofi Pasteur (Grant/Research Support) Erik Lamberth, MD, Pfizer (Employee) Allison Thompson, MD, Pfizer (Employee) Jelena Drozd, MS, Pfizer (Employee) James Trammel, MS, Pfizer (Employee) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Peter Giardina, PhD, Pfizer (Employee) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)

While widespread use of pneumococcal conjugate vaccines (PCVs) has reduced disease burden, expanding serotype coverage remains an unmet need in disease prevention. The 20-valent PCV (PCV20) contains capsular polysaccharide conjugates from serotypes included in the 13-valent PCV (PCV13; Prevnar 13®) as well as 7 additional serotypes. In a phase 2 study of PCV20 in adults 60–64 years of age, robust immune responses were observed at 1 month after vaccination; antibody persistence up to 12 months after vaccination from that study is described herein. In this randomized, active-controlled, double-blind study (ClinicalTrials.gov NCT03313037), adults aged 60–64 years received a single PCV20 dose followed 1 month later by saline placebo or PCV13 followed 1 month later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), which provided benchmarks for all PCV20 serotypes. Immunogenicity was assessed at baseline and at 1 and 12 months after vaccination as serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs). OPA and IgG geometric mean fold rises (GMFRs) from baseline to 12 months after vaccination were assessed. In the PCV20 group, OPA GMTs (n=185–200 at Month 12) for all PCV20 serotypes increased substantially from baseline to 1 month after vaccination and then declined by Month 12 but remained elevated above baseline. OPA GMFRs from baseline to Month 12 after PCV20 vaccination were 1.9–15.0 for the serotypes in common with PCV13 and 5.6–15.6 for the 7 additional serotypes. Similar results were observed for IgG concentrations, with GMFRs of 2.4–9.4 for the PCV13 serotypes and 3.0–15.5 for the 7 additional serotypes. At Month 12, 11 months after PPSV23 vaccination (n=162–195), OPA GMFRs were 5.3–11.5 for the 7 additional serotypes; IgG GMFRs were 5.0–10.4. Benchmarking to PCV13 serotypes in the control group was not appropriate as these subjects received both PCV13 and PPSV23, which overlap in polysaccharide composition for 12 serotypes. Immune responses induced by PCV20 persisted at 12 months after vaccination in adults 60–64 years of age, further supporting the potential of PCV20 to expand serotype protection against adult pneumococcal disease. Mariano Young Jr., MD, Pfizer Inc (Employee, Shareholder) Daniel Scott, MD, Pfizer (Employee, Shareholder) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Ingrid L. Scully, PhD, Pfizer Inc (Employee, Shareholder) John Ginis, BS, Pfizer Inc (Employee, Shareholder) Yahong Peng, PhD, Pfizer (Employee, Shareholder) Kathrin U. Jansen, PhD, Pfizer (Employee, Shareholder) William C. Gruber, MD, Pfizer (Employee, Shareholder) Wendy Watson, MD, Pfizer (Employee, Shareholder)