A randomized phase 1 study of the safety and immunogenicity of 2 novel pneumococcal conjugate vaccines in healthy Japanese adults in the United States

Abstract

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.

Keywords: PCV20; Streptococcus pneumoniae; cPCV7; clinical trial; immunogenicity; pneumococcal conjugate vaccine; safety.

Figure 1.

Participant Disposition. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV20 = 20-valent pneumococcal conjugate vaccine

Figure 2.

Reactogenicity Events Including (a) Local Reactions and (b) Systemic Events Occurring Up to 14 Days After Vaccination. The single report of fever (38.8°C; 1 participant in the PCV20 group) is not included. Number of participants: PCV20, n = 35; cPCV7, n = 34; PCV13, n = 34. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV20 = 20-valent pneumococcal conjugate vaccine

Figure 3.

Pneumococcal OPA GMTs and GMFRs With 2-Sided 95% CIs for Each Serotype. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis. cPCV7 = complementary 7-valent pneumococcal conjugate vaccine; GMFRs = geometric mean fold-rises from before vaccination to 1 month after vaccination; GMTs = geometric mean titers; LLOQ = lower limit of quantitation; OPA = opsonophagocytic activity; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV20 = 20-valent pneumococcal conjugate vaccine