Immunogenicity and safety of an inactivated quadrivalent influenza vaccine co-administered with a 23-valent pneumococcal polysaccharide vaccine versus separate administration, in adults ≥50years of age: Results from a phase III, randomized, non-inferiority trial.

INTRODUCTION: We compared co-administration versus separate administration of an inactivated quadrivalent influenza vaccine (IIV4) with a 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults at high risk of complications of influenza and pneumococcal infection. METHODS: This phase III, placebo-controlled, observer-blind trial (NCT02218697) was conducted in France and Belgium during the 2014-2015 influenza season. Adults≥50years of age meeting their country's vaccination recommendations were randomized 1:1 to co-administration or separate administration. Immunogenicity was assessed by hemagglutination inhibition (HI) titers for IIV4 and 22F-inhibition ELISA for PPV23. Co-primary objectives were to demonstrate non-inferiority of co-administration versus separate administration in terms of geometric mean titer (GMT) ratio for each influenza strain in the IIV4 and geometric mean concentration (GMC) ratio for six pneumococcal serotypes (1, 3, 4, 7F, 14, 19A) in the PPV23 in the per-protocol cohort (N=334). RESULTS: The study met its co-primary objectives, with the upper limit of the 95% confidence interval of the GMT and GMC ratios (separate administration over co-administration) being ≤2.0 for all four antigens of the IIV4 and the six pre-selected serotypes of the PPV23, respectively. Immunogenicity of the IIV4 and PPV23 was similar regardless of administration schedule. In a post hoc analysis pooling participants ≥60years of age from the co-administration and separate administration groups, IIV4 immunogenicity was similar in higher risk adults with comorbidities (diabetes; respiratory, heart, kidney, liver, or neurological diseases; morbid obesity) versus those without. Both vaccines had an acceptable safety and reactogenicity profile; pain was the most common symptom, occurring more often with co-administration than separate administration. CONCLUSION: The IIV4 and PPV23 can be co-administered without reducing antibody responses reflecting protection against influenza or pneumococcal disease. Co-administration of PPV23 at the annual influenza vaccination visit may improve uptake. Comorbidities had no impact on IIV4 immunogenicity, supporting its value in older adults with chronic medical conditions. Clinical Trial Registry Number: NCT02218697.