Estimating influenza vaccine efficacy from challenge and community-based study data

Abstract

In this paper, the authors provide estimates of 4 measures of vaccine efficacy for live, attenuated and inactivated influenza vaccine based on secondary analysis of 5 experimental influenza challenge studies in seronegative adults and community-based vaccine trials. The 4 vaccine efficacy measures are for susceptibility (VE(S)), symptomatic illness given infection (VE(P)), infection and illness (VE(SP)), and infectiousness (VE(I)). The authors also propose a combined (VE(C)) measure of the reduction in transmission in the entire population based on all of the above efficacy measures. Live influenza vaccine and inactivated vaccine provided similar protection against laboratory-confirmed infection (for live vaccine: VE(S) = 41%, 95% confidence interval (CI): 15, 66; for inactivated vaccine: VE(S) = 43%, 95% CI: 8, 79). Live vaccine had a higher efficacy for illness given infection (VE(P) = 67%, 95% CI: 24, 100) than inactivated vaccine (VE(P) = 29%, 95% CI: -19, 76), although the difference was not statistically significant. VE(SP) for the live vaccine was higher than for the inactivated vaccine. VE(I) estimates were particularly low for these influenza vaccines. VE(SP) and VE(C) can remain high for both vaccines, even when VE(I) is relatively low, as long as the other 2 measures of vaccine efficacy are relatively high.

Figure 1.

Point estimates and the weighted mean for the A) absolute efficacy of live influenza vaccine based on secondary analysis of the influenza challenge study data, B) absolute efficacy of inactivated influenza vaccine based on secondary analysis of the influenza challenge study data, and C) relative efficacy of live versus inactivated influenza vaccine based on secondary analysis of the influenza challenge study data. VE_I, vaccine efficacy for infection; VE_P, vaccine efficacy for illness given infection; VE_S, vaccine efficacy for susceptibility; VE_SP, vaccine efficacy for laboratory-confirmed influenza illness.

Figure 2.

Vaccine efficacy for laboratory-confirmed influenza illness (VE_SP) and combined vaccine efficacy (VE_C) as functions of vaccine efficacy for susceptibility (VE_S), vaccine efficacy for illness given infection (VE_P), and vaccine efficacy for infectiousness (VE_I). A) The curves are contours for the VE_SP as a function of VE_S and VE_P. Note that the value of the VE_SP is constant along the contour curves at the value shown; B) VE_C as a function of VE_I for different pairs of values of VE_S and VE_P; C) VE_C as a function of VE_S for different values of VE_P when VE_I is held constant at 20%; D) VE_C as a function of VE_P for different values of VE_S when VE_I is held constant at 20%. It was assumed that the pathogenicity is 67%, that is, k = 0.67 (8–10) and that unvaccinated, asymptomatic, infected people are half as infectious as symptomatic, infected people, that is, m = 0.5 (9, 10) (refer to the Appendix).