Safety, Tolerability, and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine (PCV20) in Adults 60 to 64 Years of Age

Abstract

Background: Pneumococcal conjugate vaccines (PCVs) have significantly decreased pneumococcal disease worldwide; however, expanding serotype coverage may further reduce disease burden. A 20-valent PCV (PCV20) containing capsular polysaccharide conjugates of serotypes present in the 13-valent PCV (PCV13) and 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) is currently in development. This phase 2 study evaluated safety, tolerability, and immunogenicity of PCV20 in adults without prior pneumococcal vaccination.

Methods: In this randomized, active-controlled, double-blinded trial, 444 adults 60 through 64 years of age were randomized to receive either a single dose of PCV20 followed 1 month later by saline placebo or a single dose of PCV13 followed 1 month later by 23-valent polysaccharide vaccine. Local injection site reactions, select systemic symptoms, and adverse events (AEs) were recorded. Immunogenicity was assessed by measuring serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month after each vaccination.

Results: Local reaction and systemic event rates were similar after vaccination with PCV20 or PCV13; no serious vaccine-related AEs were reported. In the PCV20 group, functional immune responses as measured by OPA were robust for all 20 serotypes included in the vaccine, with geometric mean fold rises from baseline ranging from 6.0 to 113.4.

Conclusions: PCV20 was well tolerated in adults 60 to 64 years of age, with a safety profile consistent with historical experience of PCVs in this age group. Substantial OPA responses were elicited against all serotypes. Results demonstrate the potential for PCV20 to expand pneumococcal disease protection.

Clinical trials registration: NCT03313037.

Keywords: Streptococcus pneumoniae; 20-valent pneumococcal conjugate vaccine; adult; clinical trial; immunogenicity and safety.

Figure 1.

Study design. Immune responses measured at 12 months following vaccination 1 are not reported here. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 2.

Subject disposition. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 3.

Prompted reactogenicity events including (A) local reactions within 10 days of vaccination, and (B) systemic events within 7 days of vaccination. The single report of fever is not included. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine.

Figure 4.

OPA (A) GMTs and (B) GMFRs for the PCV13 serotypes before and 1 month after vaccination. LLOQs for individual serotypes were as follows: serotype 1, 18; serotype 3, 12; serotype 4, 21; serotype 5, 29; serotype 6A, 37; serotype 6B, 43; serotype 7F, 113; serotype 9V, 141; serotype 14, 35; serotype 18C, 31; serotype 19A, 18; serotype 19F, 48; serotype 23F, 13. Abbreviations: GMFR, geometric mean fold rise; GMT, geometric mean titer; LLOQ, lower limit of quantitation; OPA, opsonophagocytic activity; PCV13, 13-valent pneumococcal conjugate vaccine; PCV20, 20-valent pneumococcal conjugate vaccine.

Figure 5.

OPA (A) GMTs and (B) GMFRs for the 7 additional serotypes before and 1 month after vaccination. LLOQs for individual serotypes were as follows: serotype 8, 16; serotype 10A, 14; serotype 11A, 32; serotype 12F, 51; serotype 15B, 36; serotype 22F, 28; serotype 33F, 49. Abbreviations: CI, confidence interval; GMFR, geometric mean fold rise; GMT, geometric mean titer; LLOQ, lower limit of quantitation; OPA, opsonophagocytic activity; PCV20, 20-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.