Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine Given Concomitantly with Trivalent Inactivated Influenza Vaccine in Healthy Adults

Background:
This study assesses compatibility of PCV13 given with TIV prior to a large-scale efficacy study against pneumonia in which both vaccines may be administered concomitantly.

Objectives:
To demonstrate that immune responses after coadministration of PCV13 and TIV are noninferior to either given alone, and to assess the safety and tolerability of coadministration.

Methods:
Subjects aged ≥65 (n=1160) were randomly assigned (1:1 ratio) to receive at 0 and 1 month PCV13+TIV followed by placebo or TIV+placebo followed by PCV13. Immune responses to TIV (A/H1N1, A/H3N2, B antigens) and PCV13 (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) were determined before and 1 month after vaccination. Local reactions and systemic events were assessed.

Results:
The percentage of evaluable subjects (PCV13+TIV n=549; TIV+placebo n=547) with a 4-fold increase in TIV antibody titer after PCV13+TIV compared to TIV+placebo was A/H1N1 80.3% vs 78.6%, A/H3N2 58.0% vs 62.6%, B 52.2% vs 54.0%. Noninferiority was met for all except A/H3N2, with lower bound of CI = -10.4%, slightly below the predefined lower limit of -10%. The percentage of subjects with HAI titers ≥40 was 94.0%, 96.5%, 81.9% for A/H1N1, A/H3N2 and B after PCV13+TIV. PCV13 IgG geometric mean (GM) concentrations 1 month after PCV13+TIV were 1.08 to 11.93 µg/mL, and 1 month after PCV13 alone were 1.15 to 17.10 µg/mL; noninferiority (GM ratio > 0.5 [2-fold criterion]) was met for all serotypes except 19F, with lower bound of CI=0.49. For PCV13+TIV compared to (1) TIV+placebo, (2) PCV13 alone, any local reactions were mainly mild: 46.9% vs (1)15.9%, (2) 46.6%; systemic events were more frequent after PCV13+TIV: 60.2% vs (1) 50.7%, (2) 48.6%.

Conclusions:
PCV13+TIV has an acceptable safety and immunogenicity profile compared to TIV or PCV13 given alone.