Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine formulations with and without aluminum phosphate and comparison of the formulation of choice with 23-valent pneumococcal polysaccharide vaccine in elderly adults: a randomized open-label trial

Abstract

This randomized open-label trial was designed to provide preliminary immunogenicity and safety data to support development of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) for adults. The aims were to: identify an age-appropriate PCV13 formulation, i.e., with (n = 309) or without (n = 304) aluminum phosphate (AlPO 4); compare the selected PCV13 formulation (n = 309) with 23-valent pneumococcal polysaccharide vaccine (PPSV23; n = 301); and, together with an extension study, assess sequential use of pneumococcal vaccines at 1-year intervals in adults aged ≥65 years (n = 105) not pre-vaccinated with PPSV23. Immune responses were measured by ELISA and opsonophagocytic activity assays 1 month postvaccination. Immunoglobulin G responses elicited by PCV13 with AlPO 4 and PCV13 without AlPO 4 were similar for the majority, and noninferior for all PCV13 serotypes. PCV13 with AlPO 4 was generally more reactogenic, with reactions mainly mild or moderate. Thus, PCV13 with AlPO 4 (hereafter PCV13) became the selected formulation. Immune responses to PCV13 were noninferior for all but one serotype and for most PCV13 serotypes superior to PPSV23. Vaccine sequence assessments showed that for PCV13/PPSV23, the initial PCV13 dose generally enhanced responses to a subsequent PPSV23 dose, compared with PPSV23 alone. For PCV13/PCV13, a second dose did not enhance the first dose response when given after 1 year. For PCV13/PPSV23/PCV13, priming with PCV13 (vaccination 1) did not protect against lower responses induced by PPSV23 to subsequent PCV13 (vaccination 3). In conclusion, the pediatric PCV13 formulation with AlPO 4 is well tolerated and immunogenic in adults, is generally more immunogenic than PPSV23, and subsequent vaccination with PPSV23 is possible if required.

Trial registration: ClinicalTrials.gov NCT00269672 NCT00500357.

Keywords: 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; PCV13; PPSV23; adults; elderly; immunogenicity; safety.

Figures

Figure 1. CONSORT diagram showing disposition of study participants. Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 2. Local reactions reported within 14 d after vaccination. aSeverity of redness and swelling: absent (no or minimal redness/swelling present, 0 to <2.5 cm; 0 to <5 caliper units), mild (2.5–5.0 cm; ≥5 to ≤10 caliper units), moderate (5.1–10.0 cm; >10 to ≤20 caliper units), or severe (>10.0 cm; >20 caliper units). bSeverity of pain at the injection(s) site: mild (awareness of sign/symptom but easily tolerated), moderate (enough discomfort to interfere with usual activity), or severe (inability to do usual activity).cSeverity of limitation of arm movement: absent (no limitation), mild (some limitation), moderate (able to move arm above shoulder-level but not above head), or severe (unable to move arm above shoulder). Abbreviations: PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.