Table 4.

Mediation effect estimates for D29 quantitative markers with 95% confidence intervals

VE against severe-critical COVID-19
	Non-Marker Mediated VE (95% CI)	Marker Mediated VE (95% CI)	Prop. Mediated (95% CI)
nAb-ID50 (IU50/ml)	0.645 (0.311, 0.817)	0.340 (0.166, 0.477)	0.286 (0.085, 0.487)
Spike IgG (BAU/ml)	0.667 (0.191, 0.863)	0.297 (−0.349, 0.634)	0.243 (−0.214, 0.700)
RBD IgG (BAU/ml)	0.696 (0.257, 0.876)	0.228 (−0.497, 0.602)	0.179 (−0.282, 0.639)
VE against moderate COVID-19
	Non-Marker Mediated VE (95% CI)	Marker Mediated VE (95% CI)	Prop. Mediated (95% CI)
nAb-ID50 (IU50/ml)	0.196 (−0.048, 0.383)	0.199 (0.017, 0.348)	0.505 (0.008, 1.00)
Spike IgG (BAU/ml)	−0.013 (−0.605, 0.361)	0.365 (0.031, 0.583)	1.03 (−0.022, 2.08)
RBD IgG (BAU/ml)	0.063 (−0.410, 0.377)	0.313 (0.002, 0.527)	0.852 (−0.051, 1.76)

Non-marker mediated VE = VE comparing vaccine vs. placebo with antibody marker set to value if assigned placebo.

Marker-mediated VE = VE in vaccinated comparing observed antibody marker vs. hypothetical marker had the participant received placebo.

Prop. Mediated = fraction of total risk reduction from vaccine attributed to the antibody marker.

BAU, antibody binding units; IU, international units; nAb-ID50, 50% inhibitory dilution neutralizing antibody.

Overall VE (95% CI) against the severe-critical, moderate, and moderate to severe-critical endpoints starting 7 days post-D29 through 220 days post-vaccination was 73.1% (58.7%, 84.1%), 41.3% (28.6%, 51.3%), and 48.6% (38.6%, 57.0%), respectively.

Proportion mediated is not a true proportion in that it can take values outside of [0, 1]. Proportion mediated = 1 is equivalent to Non-marker-mediated VE = 0% and Proportion mediated = 0 is equivalent to Non-marker-mediated VE = Overall VE.