medRxiv. 2022 Apr 12; NA(NA):NA.

PubMed ID: 35441174

Immune correlates analysis of a single Ad26.COV2.S dose in the ENSEMBLE COVID-19 vaccine efficacy clinical trial

Fong Y, McDermott AB, Benkeser D, Roels S, Stieh DJ, Vandebosch A, Le Gars M, Van Roey GA, Houchens CR, Martins K, Jayashankar L, Castellino F, Amoa-Awua O, Basappa M, Flach B, Lin BC, Moore C, Naisan M, Naqvi M, Narpala S, O'Connell S, Mueller A, Serebryannyy L, Castro M, Wang J, Petropoulos CJ, Luedtke A, Hyrien O, Lu Y, Yu C, Borate B, van der Laan LWP, Hejazi NS, Kenny A, Carone M, Wolfe DN, Sadoff J, Gray GE, Grinsztejn B, Goepfert PA, Little SJ, de Sousa LP, Maboa R, Randhawa AK, Andrasik MP, Hendriks J, Truyers C, Struyf F, Schuitemaker H, Douoguih M, Kublin JG, Corey L, Neuzil KM, Carpp LN, Follmann D, Gilbert PB, Koup RA, Donis RO, Janssen Team, Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team, United States Government (USG)/CoVPN Biostatistics Team

Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.