Efficacy studies of influenza vaccines: effect of end points used and characteristics of vaccine failures

Abstract

Background: End points used to detect influenza in vaccine efficacy trials have varied. Both the inactivated and live attenuated influenza vaccines are efficacious; however, failure to protect occurs.

Methods: We compared characteristics of influenza A (H3N2) and B cases from 3 years of a comparative placebo-controlled trial of inactivated and live attenuated vaccines, and we evaluated the laboratory end points used to determine efficacy.

Results: Although illness duration and reported symptoms did not differ by intervention, subjects with influenza in the inactivated vaccine group were less likely than those in the placebo group to report medically attended illnesses. All influenza type A (H3N2) and B cases isolated in cell culture were also identified by real-time polymerase chain reaction (rtPCR). However, only 69% of type A (H3N2) cases identified by rtPCR also were isolated in cell culture. Isolation frequency was lowest among live attenuated vaccine failures, a reflection of lower specimen viral loads. Among cases of rtPCR identified influenza A (H3N2), 90% of placebo and 87% of live attenuated vaccine recipients but only 23% of inactivated vaccine recipients demonstrated serologic confirmation of infection.

Conclusions: In influenza vaccine efficacy studies, virus identification using rtPCR is the ideal end point. Isolation in cell culture will miss cases, and a serologic end point alone will overestimate inactivated vaccine efficacy.

Trial registration: ClinicalTrials.gov NCT00133523 NCT00538512.

Figure 1.

The proportion of cases confirmed as influenza types A (H3N2) or B that were isolated in cell culture by cycle threshold (Ct) category indicating high (Ct, < 25), medium (Ct, 25–30), and low (Ct, >30 to < 40) specimen viral loads. rtPCR, real-time polymerase chain reaction.