In this study, which included predominantly white adults aged ≥65

In this study, which included predominantly white adults aged ≥65 years who were

naïve to PPV, the immunogenicity and safety responses to the three viral subtypes in TIV (A/H1N1, A/H3N2, and B) and each CT99021 concentration of the 13 serotypes (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in PCV13 after concomitant administration of PCV13 and TIV were directly compared with TIV (and placebo) or PCV13 administered after TIV. A clinically meaningful, empirically determined level of antibodies against pneumococcal or influenza antigens that is protective against disease in adults is lacking. A correlation between antibody levels and protection against invasive pneumococcal disease was demonstrated previously in learn more children [18]. Therefore, as in most vaccine trials, the endpoints of the present trial were based on a comparison of the relative changes in immune response between administration of the vaccines separately or together [19], [20] and [21].

For TIV antigens, the immune response correlates of protection are considered to be acceptable levels of serum antibody to the individual vaccine hemagglutinins as measured by HAI and described in “Note for Guidance on Harmonisation of Requirements for Influenza Vaccines” [16]. The analysis of TIV (A/H1N1, A/H3N2, and B) immune responses, based on the proportion of responders achieving at least a 4-fold rise in HAI titre, showed that noninferiority of PCV13 + TIV relative to TIV was met for A/H1N1 and B; for A/H3N2, the difference in proportions of responders was −4.6%, with a lower limit of the 95% CI of −10.4%, which was slightly lower than the more than −10.0% predefined margin of noninferiority. However, it was noted that in contrast

with the other two virus subtypes, the mean predose-1 titres for A/H3N2 were quite high, perhaps reflecting aminophylline pressure from A/H3N2 epidemics that occurred in the years prior to the study. In the regions where the study was conducted, H3N2 predominated over H1N1 and B in the 2006–2007 season [22]. Higher pre-immunization titres may limit the likelihood of demonstrating 4-fold responses, and the lower frequency of response would be expected to impact the ability to demonstrate noninferiority. Notably, H3N2 responder rates at an HAI titre ≥40 were comparable in the PCV13 + TIV and Placebo + TIV groups, indicating a high likelihood of protection against H3N2. In fact, all criteria proposed in the EMA “Note for Guidance on Harmonisation of Requirements for Influenza Vaccines” [16] were exceeded for all three TIV antigens (H1N1, H3N2, and B) when TIV was administered with PCV13. The data support the conclusion that TIV is sufficiently immunogenic when given concomitantly with PCV13, and that protection against influenza is likely to be clinically indistinguishable from that provided by TIV alone.

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