TOPLINE:

Sequential administration of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) led to nonsignificant increases in memory B cells by week 28 in older adults; however, it elicited more sustained long-term immune responses against key pneumococcal serotypes than either the simultaneous or single-dose schedule. All regimens were safe and well tolerated.

METHODOLOGY:

• Researchers conducted a phase 4 randomized controlled trial to evaluate increase in antigen-specific memory B-cell responses against clinically important pneumococcal vaccine serotypes across three vaccination schedules — single, simultaneous, and sequential — in older adults.
• They enrolled 123 vaccine-naive adults (median age, 65 years; 61.8% women) who were randomly assigned to one of the three vaccination groups:
  • Simultaneous group: received both PCV13 and PPSV23 on day 0
  • Sequential group: received PCV13 on day 0, followed by PPSV23 at 6 months
  • Single group: received only PPSV23 on day 0
• The primary outcome was the change in memory B-cell counts specific for four vaccine serotypes (3, 14, 19A, and 23F) from baseline to 27-28 weeks after the first dose.
• Secondary outcomes included long-term changes in memory B-cell counts and serotype-specific immunoglobulin G levels over 24 months.

TAKEAWAY:

• From baseline to week 27-28, increases in serotype-specific memory B cells were overall minimal; however, most pronounced rise was seen in serotype 19A-specific B-cell counts — median, 0.022% (95% CI, 0.002%-0.045%) with simultaneous dosing and 0.022% (95% CI, -0.006% to 0.068%) with sequential dosing.
• At 7-14 days after completing the full vaccination schedule, increases in memory B cells were comparable across all serotypes in the simultaneous and sequential groups; however, at 6 months, the memory B-cell response for serotype 19A was lower in the simultaneous group than in the sequential group (median, -0.039%; 95% CI, -0.071% to -0.010%).
• At 24 months, the sequential group achieved higher immunoglobulin G levels against serotype 3 than both the simultaneous and single vaccination groups and had higher immunoglobulin G levels against serotype 4 than the single group.
• All vaccination schedules were well tolerated, with comparable rates of severe adverse reactions.

IN PRACTICE:

“Simultaneous pneumococcal vaccination was safe but did not elicit higher memory B-cell responses compared to sequential or single vaccination,” the authors of the study wrote.

SOURCE:

This study was led by Christina Bahrs, Institute of Infectious Diseases and Infection Control, Jena University Hospital/Friedrich-Schiller-University, Jena, Germany. It was published online on August 23, 2025, in Clinical Microbiology and Infection.

LIMITATIONS:

This study was constrained by its single-center design and limited sample size. Clinical endpoints were not evaluated, and prepandemic effects were not compared with pandemic effects. Additionally, certain PPSV23 serotypes were excluded from the analysis, and a standard method for testing immunogenicity was not used.

DISCLOSURES:

This study was supported by the German Federal Ministry of Education and Research. Some authors disclosed serving on the scientific advisory board of, receiving personal fees or speaker fees for lectures from, or receiving support for meetings and travel from GlaxoSmithKline and Pfizer.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.