A randomized phase 1/2 study of the safety and immunogenicity of a multivalent pneumococcal conjugate vaccine in healthy adults 50 through 85 years of age

Brandon Essink, James Peterson, Kari Yacisin, Himal Lal, Sarah Mirza, Xia Xu, Ingrid L Scully, Daniel A Scott, William C Gruber, Kathrin U Jansen, Wendy Watson, Brandon Essink, James Peterson, Kari Yacisin, Himal Lal, Sarah Mirza, Xia Xu, Ingrid L Scully, Daniel A Scott, William C Gruber, Kathrin U Jansen, Wendy Watson

Abstract

Pneumococcal disease can be serious and debilitating in older adults. Pneumococcal conjugate vaccines (PCVs), such as the 13-valent PCV (PCV13), reduce pneumococcal disease rates caused by vaccine serotypes. Development of PCVs offering additional coverage against serotypes not contained in PCV13 can reduce disease burden further. The complementary 7-valent PCV (cPCV7) contains seven non-PCV13 serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) and can expand coverage by supplementing direct or indirect protection from existing PCVs. This phase 1/2, randomized, active-controlled, observer-blinded study evaluated cPCV7 safety and immunogenicity in healthy adults 50-85 years of age. Stage 1 randomized 66 healthy adults (50-64 years) naive to pneumococcal vaccines to receive cPCV7 or licensed tetanus, diphtheria, and acellular pertussis vaccine; Stage 2 randomized 445 healthy adults (65-85 years) previously vaccinated with PCV13 to receive cPCV7 or 23-valent polysaccharide vaccine. Local reactions and systemic events up to 14 days and adverse events (AEs) through 1 month after vaccination were assessed. Immunogenicity was evaluated by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination (and after 12 months in Stage 2). Rates of local reactions, systemic events, and AEs were generally similar after receipt of cPCV7 or control. Robust OPA responses were observed for all seven serotypes 1 month after cPCV7; titers declined yet remained above baseline 12 months after vaccination. Overall, this study found that in adults ≥50 years of age, cPCV7 was safe, well tolerated, and elicited functional immune responses to vaccine serotypes. ClinicalTrials.gov: NCT03313050.

Keywords: Clinical trial; Streptococcus pneumoniae; pneumococcal conjugate vaccine.

Figures

Figure 1.
Figure 1.
Stage 2 subject disposition. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine
Figure 2.
Figure 2.
Reactogenicity events including (A) local reactions and (B) systemic events occurring within 14 days after vaccination (Stage 2). Three reports of fever (1 and 2 participants in cPCV7 and PPSV23 groups, respectively) are not shown. Number of participants: cPCV7, n = 221; PPSV23, n = 223. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine
Figure 3.
Figure 3.
Pneumococcal OPA GMTs before and 1 month after vaccination and GMFRs 1 month after vaccination for the cPCV7 serotypes (Stage 2). The LLOQs for each serotype were as follows: 8, 16; 10A, 14; 11A, 32; 12F, 51; 15B, 36; 22F, 28; 33F, 49. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; GMTs = geometric mean titers; GMFRs = geometric mean fold-rises; LLOQ = lower limit of quantitation; OPA = opsonophagocytic activity; PPSV23 = 23-valent pneumococcal polysaccharide vaccine
Figure 4.
Figure 4.
Pneumococcal OPA GMT antibody response curves and OPA GMFRs for the cPCV7 serotypes from baseline to 12 months after vaccination (Stage 2). Note that the y-axis scales for each graph differ. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; GMT = geometric mean titer; OPA = opsonophagocytic activity; PPSV23 = 23-valent pneumococcal polysaccharide vaccine

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