13-valent Pneumococcal Conjugate Vaccine Serotypes Research Articles

P05 Safety, tolerability, and immunogenicity of V114 compared with PCV13 in preterm infants: a pooled subgroup analysis of four Phase III studies

Abstract Background Risk of invasive pneumococcal disease is 3-fold higher in preterm versus full-term infants, mainly due to underlying comorbidities and immunological immaturity. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 serotypes in 13-valent PCV (PCV13) plus two additional serotypes, 22F and 33F. A pooled subgroup analysis was performed in preterm infants (<37 weeks gestational age) enrolled in 4 paediatric Phase III studies evaluating the safety and immunogenicity of different 4-dose regimens of V114 or PCV13. Methods Safety was evaluated as the proportion of participants with AEs following each vaccination. Serotype-specific anti-pneumococcal IgG GMCs, IgG response rates, and OPA GMTs were measured at 30 days post-primary series (PPS; post-dose 3 [PD3]), pre-toddler dose, and 30 days post-toddler dose (PTD; post-dose 4 [PD4]). Results 174 and 180 participants received V114 and PCV13, respectively. Mean gestational age was 35.4 weeks (range: 27–37 weeks). Proportions of participants with any AE were comparable between vaccination groups following each vaccination; most solicited AEs were transient (≤3 days) and of mild-to-moderate intensity. V114-elicited IgG GMCs (Figure 1), IgG response rates, and OPA GMTs were generally comparable to PCV13 for the 13 shared serotypes and higher for serotypes 22F and 33F at 30 days PPS (PD3) and PTD (PD4). Conclusions In preterm infants, vaccination with V114 has an acceptable safety profile, is well tolerated, and induces comparable immune responses to PCV13 for the 13 shared serotypes and higher immune responses to V114 serotypes 22F and 33F. Study results support use of V114 in preterm infants.

930 SAFETY, TOLERABILITY AND IMMUNOGENICITY OF 15-VALENT PNEUMOCOCCAL CONJUGATE VACCINE + PPV23 12 MONTHS LATER IN HEALTHY ADULTS ≥ 50

Abstract Background Older adults are at increased risk of pneumococcal disease (PD). V114, an investigational 15-valent Pneumococcal Conjugate Vaccine (PCV), contains all serotypes in 13-valent PCV (PCV13) plus serotypes 22F and 33F. This phase 3 trial evaluated the safety, tolerability and immunogenicity of V114 or PCV13 followed 12 months later by PPSV23 in healthy adults aged ≥50 years. Materials/Method 652 eligible adults were randomised 1:1 to receive V114 or PCV13 followed by PPSV23 12 months later. Solicited and non-solicited adverse events (AEs) were collected after each vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were measured at Day 1, Day 30, Month 12 and Month 13. Results The most common solicited AEs following PCV were injection-site pain, fatigue and myalgia; higher proportions of participants with solicited AEs were observed in the V114 group; however, the differences were not clinically significant, as most AEs were mild and of short duration. The most common solicited AEs following PPSV23 were injection-site pain, injection-site swelling, fatigue and myalgia; these events were comparable across both intervention groups. The proportion of participants with serious AEs were low in both groups and none reported to be vaccine related. No deaths occurred during the study. Serotype-specific OPA geometric mean titres (GMTs) and IgG geometric mean concentrations (GMCs) were comparable between the groups for all 15 serotypes 30 days post-vaccination with PPSV23. OPA GMTs and IgG GMCs were comparable between PCV groups for the 13 shared serotypes and higher in V114 than PCV13 for serotypes 22F and 33F 30 days and 12 months post-vaccination with PCV. V114 elicited an immune response that persisted for at least 12 months. Conclusion Sequential administration of V114 and PPSV23 is well tolerated, immunogenic and generally comparable to PCV13 followed by PPSV23 in healthy adults ≥50 years of age.

Estimates of the Health and Economic Burden of Pneumococcal Infections Attributable to the 15-Valent Pneumococcal Conjugate Vaccine Serotypes in the USA.

IntroductionDespite the availability of vaccines, pneumococcal disease (PD) is associated with high clinical and economic burden, mainly caused by non-vaccine serotypes and certain vaccine-type serotypes. V114 is a 15-valent pneumococcal conjugate vaccine (PCV) that contains two epidemiologically important serotypes, 22F and 33F, in addition to the 13 serotypes in 13-valent PCV (PCV13). This study quantified the epidemiologic and economic burden of PD attributable to V114 serotypes among adults in the USA.MethodsA Markov model was used to estimate the burden of V114 serotypes in a hypothetical, non-vaccinated cohort of US adults ≥ 19 years of age who were tracked from 2019 until death. The model calculated all the invasive pneumococcal disease (IPD) and non-bacteremic pneumococcal pneumonia (NBPP) cases, deaths, and costs. Economic burden was estimated from a healthcare payer perspective (2019 US dollars) and discounted at 3%.ResultsThe model estimated 415,229 and 10.3 million lifetime cases of V114-type IPD and NBPP, respectively. Serotypes 22F and 33F caused approximately 33% of IPD cases and 20% of NBPP cases, while serotype 3 accounted for approximately 36% of IPD cases and 13% of NBPP cases. V114 serotypes caused 472,063 total lifetime deaths. Total discounted lifetime costs attributable to V114 serotypes were $44.8 billion US dollars.ConclusionsIn this hypothetical model of a non-vaccinated cohort of US adults, V114 serotypes were associated with a substantial health and economic burden, the majority of which was attributable to serotypes 3, 22F, and 33F. The addition of V114 to the national vaccination recommendations may help to reduce the epidemiologic and economic burden associated with PD in adults ≥ 19 years of age in the USA by providing increased coverage of these serotypes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00588-x.

1050. Phase 3 Trial to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by 23valent Pneumococcal Polysaccharide Vaccine 6 Months Later in At-risk Adults Aged 18–49 Years (PNEU-DAY): A Subgroup Analysis by Baseline Risk Factors

BackgroundRisk factors (RFs) for pneumococcal disease (PD) in immunocompetent individuals include comorbidities, behavioral habits, or living in a community with increased risk of PD transmission. RF stacking of comorbidities is associated with a higher incidence of PD, approaching that of immunocompromised individuals. Pneumococcal vaccination of certain adults is recommended with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone/sequentially with pneumococcal conjugate vaccine (PCV). V114, an investigational 15-valent PCV, contains 2 epidemiologically important serotypes (STs), 22F and 33F, in addition to the 13 STs in 13-valent PCV (PCV13). MethodsPNEU-DAY was a Phase 3 study evaluating V114 or PCV13 administered on Day 1, and PPSV23 given 6 months later, in adults aged 18–49 years with or without RFs. This subgroup analysis assessed safety, tolerability, and immunogenicity of V114 and PCV13 based on the number of baseline PD RFs, which included chronic liver, lung, and heart disease, diabetes mellitus, tobacco use, and alcohol consumption. Adverse events (AEs; overall and solicited) were collected after each vaccination. Immunogenicity assessment was based on ST-specific opsonophagocytic activity (OPA) at 30 days after each vaccination. Subgroup analyses were conducted by RF group (0, 1, or ≥2 RFs for PD).ResultsAmong the 1515 participants randomized to V114 (n=1135) or PCV13 (n=380), 25.2% had no RFs, 54.7% had 1 RF and 20.1% had ≥2 RFs for PD at baseline. The proportions of participants with solicited AEs following V114/PCV13 and PPSV23 were comparable across the 3 subgroups, with injection-site pain, myalgia, and fatigue being the most common. V114 and PCV13 were immunogenic in all subgroups based on OPA geometric mean titers (GMTs) at 30 days post-vaccination for the 13 shared STs (Figure); in addition, V114 induced a robust immune response to the 2 unique STs (22F, 33F) in all subgroups. PPSV23 following PCV was immunogenic for all 15 STs contained in V114 across all subgroups.Figure. Serotype-specific OPA GMTs at baseline and 30 days post-vaccination with V114 and PCV13 by number of baseline risk factors (per-protocol population) ConclusionV114 administered alone/sequentially with PPSV23 is well tolerated and immunogenic for all 15 vaccine STs, including those not contained in PCV13, in immunocompetent adults aged 18–49 years, regardless of the number of baseline RFs.Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Francisco J. Pasquel, MD, MPH, Boehringer Ingelheim (Consultant)Dexcom (Grant/Research Support)Eli Lilly & Company (Consultant)Insulet (Grant/Research Support)Merck & Co., Inc. (Consultant, Grant/Research Support) K. Rajender Reddy, MD, BMS (Grant/Research Support)Deciphera (Advisor or Review Panel member)Gilead (Grant/Research Support)Grifols (Grant/Research Support)HCC-TARGET (Grant/Research Support)Intercept (Grant/Research Support)Mallinckrodt (Grant/Research Support, Advisor or Review Panel member)NASH-TARGET (Grant/Research Support)Pfizer (Advisor or Review Panel member)Sequana (Grant/Research Support) Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Rachel Dawson, D.O. MPH, Merck & Co., Inc. (Employee, Shareholder) Jennifer McCauley, BSc, Merck & Co., Inc. (Employee) Kyeongmi Cheon, Ph.D., Merck & Co., Inc. (Employee, Shareholder) Alison Pedley, PhD, Merck & Co., Inc. (Employee) Tina Sterling, BS, Merck & Co., Inc. (Employee, Shareholder) Gretchen Tamms, B.S., Merck Sharp and Dohme (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Ulrike K. Buchwald, MD, MS, Merck & Co., Inc. (Employee)TB Alliance (Employee)

Health and economic burden associated with 15-valent pneumococcal conjugate vaccine serotypes in children in the United States

Aims V114 is an investigational 15-valent pneumococcal conjugate vaccine (PCV) containing the 13 Streptococcus pneumoniae serotypes in 13-valent PCV (PCV13) plus two additional serotypes. This study quantified the health and economic burden of invasive pneumococcal disease (IPD) and acute otitis media (AOM) caused by V114 types among children in the United States. Materials and methods A Markov model estimated the number of V114-type IPD and AOM cases and costs in a hypothetical, unvaccinated US birth cohort over 20 years. Three time periods were analyzed using time-specific epidemiological data to determine the number of IPD and AOM cases associated with all 15 serotypes in V114. The time periods were: (1) pre-PCV7 (1999); (2) pre-PCV13 (2009); (3) post-PCV13 (2017). Costs were estimated from a societal perspective (2018 US dollars) and discounted at 3%. Results The model estimated 18,983 IPD cases and 5.4 million AOM cases associated with V114 serotypes pre-PCV7, 4,697 IPD cases and 3.0 million AOM cases pre-PCV13, and 948 IPD cases and 0.2 million AOM cases post-PCV13. Total discounted costs associated with V114 serotypes were $1.7 billion pre-PCV7, $730 million pre-PCV13, and $75 million US dollars post-PCV13. Limitations Post-meningitis sequelae, cases of non-bacteremic pneumonia, and direct non-medical costs were not included. Conclusions IPD and AOM cases and costs were estimated in a hypothetical US birth cohort followed for 20 years at three time periods. In all three periods, the serotypes targeted by V114 contributed to significant morbidity and costs. New pediatric pneumococcal vaccines must continue to retain serotypes in licensed vaccines to maintain disease reduction while extending coverage to non-vaccine serotypes.

Pharyngeal colonization by Streptococcus pneumoniae in older children and adolescents in a geographical area characterized by relatively limited pneumococcal vaccination coverage.

The aim of this study was to evaluate the relation between colonization and vaccination status with pneumococcal conjugate vaccine (PCV) in older children and adolescents living in an area characterized by relatively limited vaccination coverage. Oropharyngeal swabs were obtained from 2076 randomly selected healthy school-age children and adolescents, and the extracted genomic DNA was tested for Streptococcus pneumoniae by means of real-time polymerase chain reaction. All of the positive cases were subsequently serotyped, and the association between vaccination status with the heptavalent PCV (PCV7) and pneumococcal colonization was determined. S. pneumoniae was identified in the oropharyngeal swabs of 1201 subjects (57.9%), and its prevalence declined with age (74.9% in subjects aged <10 years, 51.8% in those aged 10-14 years and 32.7% in those aged ≥15 years; P < 0.001). There were more carriers of any pneumococcal serotype, any of the serotypes in PCV7, or any of the 6 additional serotypes in 13-valent PCV (PCV13) among the vaccinated than the unvaccinated subjects, but no association emerged after adjustment for age and other selected covariates. Sub-analyses by serotype and age groups revealed significant differences in the case of serotypes 3 and 19A among children aged <10 years (odds ratios of 2.03 and 2.18, respectively). These results show the absence of any long-term effect of PCV7 on colonization, and raise doubts concerning the recent suggestion to use carriage to evaluate the efficacy of PCVs. The high prevalence of carriers in all of the age groups independent of previous pneumococcal vaccination indicates that further studies are needed to evaluate whether the extensive use of PCVs in healthy older children and adolescents might reduce pharyngeal colonization of these subjects thereby increasing herd immunity.