TY - JOUR
T1 - A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED)
AU - for the V114-029 PNEU-PED study group
AU - Lupinacci, Robert
AU - Rupp, Richard
AU - Wittawatmongkol, Orasri
AU - Jones, Jake
AU - Quinones, Jeffrey
AU - Ulukol, Betul
AU - Dagan, Ron
AU - Richmond, Peter
AU - Stek, Jon E.
AU - Romero, Lizbeth
AU - Koseoglu, Sandra
AU - Tamms, Gretchen
AU - McFetridge, Richard
AU - Li, Jianing
AU - Cheon, Kyeongmi
AU - Musey, Luwy
AU - Banniettis, Natalie
AU - Bickham, Kara
N1 - Publisher Copyright:
© 2023 Merck Sharp & Dohme LLC., a subsidiary Merck & Co., Inc., The Author(s)
PY - 2023/1/27
Y1 - 2023/1/27
N2 - Background: Pneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs) confer protection against PD caused by most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and additional serotypes 22F and 33F. This pivotal phase 3 study compared safety and immunogenicity of V114 and PCV13. Methods: 1720 healthy infants were randomized 1:1 to receive a 4-dose regimen of V114 or PCV13 concomitantly with other routine pediatric vaccines. Safety was evaluated after each dose as proportion of participants with adverse events (AEs). Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured at 1-month post-dose 3 (PD3), pre-dose 4, and 1-month post-dose 4 (PD4). IgG response rates, geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) were compared between vaccination groups. Results: The proportion, maximum intensity, and duration of injection-site, systemic, and serious AEs were generally comparable between V114 and PCV13 groups. In comparison to PCV13, V114 met non-inferiority criteria for all 15 serotypes based on IgG response rates at PD3. V114 met non-inferiority criteria by IgG GMCs for all serotypes at PD3 and PD4, except for serotype 6A at PD3. V114-induced antibodies had bactericidal activity as assessed by OPA. Further, V114 met superiority criteria for shared serotype 3 and unique serotypes 22F and 33F compared to PCV13 by serotype-specific IgG GMCs at both PD3 and PD4. Immunogenicity of concomitantly administered routine pediatric vaccines was comparable in V114 and PCV13 groups. Conclusions: In healthy infants, V114 displays acceptable safety and tolerability profiles and generates comparable immune responses to PCV13. V114 also met superiority criteria for serotypes 3, 22F, and 33F. These results support use of V114 for prevention of PD as part of routine infant vaccination schedules. Trial registration: ClinicalTrials.gov: NCT03893448; EudraCT: 2018-004109-21.
AB - Background: Pneumococcal disease (PD) remains a major health concern with considerable morbidity and mortality in children. Currently licensed pneumococcal conjugate vaccines (PCVs) confer protection against PD caused by most vaccine serotypes, but non-vaccine serotypes contribute to residual disease. V114 is a 15-valent PCV containing all 13 serotypes in Prevnar 13™ (PCV13) and additional serotypes 22F and 33F. This pivotal phase 3 study compared safety and immunogenicity of V114 and PCV13. Methods: 1720 healthy infants were randomized 1:1 to receive a 4-dose regimen of V114 or PCV13 concomitantly with other routine pediatric vaccines. Safety was evaluated after each dose as proportion of participants with adverse events (AEs). Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured at 1-month post-dose 3 (PD3), pre-dose 4, and 1-month post-dose 4 (PD4). IgG response rates, geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) were compared between vaccination groups. Results: The proportion, maximum intensity, and duration of injection-site, systemic, and serious AEs were generally comparable between V114 and PCV13 groups. In comparison to PCV13, V114 met non-inferiority criteria for all 15 serotypes based on IgG response rates at PD3. V114 met non-inferiority criteria by IgG GMCs for all serotypes at PD3 and PD4, except for serotype 6A at PD3. V114-induced antibodies had bactericidal activity as assessed by OPA. Further, V114 met superiority criteria for shared serotype 3 and unique serotypes 22F and 33F compared to PCV13 by serotype-specific IgG GMCs at both PD3 and PD4. Immunogenicity of concomitantly administered routine pediatric vaccines was comparable in V114 and PCV13 groups. Conclusions: In healthy infants, V114 displays acceptable safety and tolerability profiles and generates comparable immune responses to PCV13. V114 also met superiority criteria for serotypes 3, 22F, and 33F. These results support use of V114 for prevention of PD as part of routine infant vaccination schedules. Trial registration: ClinicalTrials.gov: NCT03893448; EudraCT: 2018-004109-21.
KW - Immunogenicity
KW - Pediatric
KW - Pneumococcal vaccine
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85146071439&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2022.12.054
DO - 10.1016/j.vaccine.2022.12.054
M3 - Article
C2 - 36621410
AN - SCOPUS:85146071439
SN - 0264-410X
VL - 41
SP - 1142
EP - 1152
JO - Vaccine
JF - Vaccine
IS - 5
ER -