Article
Author: Van Dromme, Ilse ; Martins, Karen ; Castellino, Flora ; Douoguih, Macaya ; Narpala, Sandeep ; Carpp, Lindsay N. ; Koup, Richard A ; Randhawa, April K. ; Benkeser, David ; Fong, Youyi ; Flach, Britta ; Corey, Lawrence ; Donis, Ruben O ; O'Connell, Sarah ; Sadoff, Jerald ; Kublin, James G. ; Luedtke, Alex ; Mueller, Allen ; Goepfert, Paul A. ; Lin, Bob C. ; Stieh, Daniel J. ; Hyrien, Ollivier ; O’Connell, Sarah ; Wolfe, Daniel N. ; Carpp, Lindsay N ; Wang, Jennifer ; Koup, Richard A. ; McDermott, Adrian B ; Hejazi, Nima S. ; Gaur, Aditya H ; Basappa, Manjula ; Schuitemaker, Hanneke ; Lu, Yiwen ; Gilbert, Peter B. ; Hendriks, Jenny ; Wolfe, Daniel N ; Andrasik, Michele P ; Bekker, Linda-Gail ; Vandebosch, An ; Goepfert, Paul A ; Lin, Bob C ; Stieh, Daniel J ; Neuzil, Kathleen M. ; Petropoulos, Christos J. ; Carone, Marco ; Kenny, Avi ; Gilbert, Peter B ; Huang, Ying ; Houchens, Christopher R ; McDermott, Adrian B. ; Van Roey, Griet A. ; Naqvi, Muhammed ; Roels, Sanne ; Houchens, Christopher R. ; Hejazi, Nima S ; Gaur, Aditya H. ; Randhawa, April K ; Gray, Glenda E ; Juraska, Michal ; Petropoulos, Christos J ; Struyf, Frank ; Jayashankar, Lakshmi ; Truyers, Carla ; Andrasik, Michele P. ; Serebryannyy, Leo ; Veloso, Valdilea G. ; Gray, Glenda E. ; Donis, Ruben O. ; Veloso, Valdilea G ; Grinsztejn, Beatriz ; Yu, Chenchen ; Neuzil, Kathleen M ; Amoa-Awua, Obrimpong ; Castro, Mike ; Kublin, James G ; Van Roey, Griet A ; Naisan, Mursal ; Moore, Christopher ; Follmann, Dean
Abstract:Assessment of immune correlates of severe COVID-19 has been hampered by the low numbers of severe cases in COVID-19 vaccine efficacy (VE) trials. We assess neutralizing and binding antibody levels at 4 weeks post-Ad26.COV2.S vaccination as correlates of risk and of protection against severe-critical COVID-19 through 220 days post-vaccination in the ENSEMBLE trial (NCT04505722), constituting ~4.5 months longer follow-up than our previous correlates analysis and enabling inclusion of 42 severe-critical vaccine-breakthrough cases. Neutralizing antibody titer is a strong inverse correlate of severe-critical COVID-19, with estimated hazard ratio (HR) per 10-fold increase 0.35 (95% CI: 0.13, 0.90). In a multivariable model, HRs are 0.31 (0.11, 0.89) for neutralizing antibody titer and 1.22 (0.49, 3.02) for anti-Spike binding antibody concentration. VE against severe-critical COVID-19 rises with neutralizing antibody titer: 63.1% (95% CI: 40.0%, 77.3%) at unquantifiable [<4.8975 International Units (IU)50/ml], 85.2% (47.2%, 95.3%) at just-quantifiable (5.2 IU50/ml), and 95.1% (81.1%, 96.9%) at 90th percentile (30.2 IU50/ml). At the same titers, VE against moderate COVID-19 is 32.5% (11.8%, 48.4%), 33.9% (19.1%, 59.3%), and 60.7% (40.4%, 76.4%). Protection against moderate vs. severe disease may require higher antibody levels, and very low antibody levels and/or other immune responses may associate with protection against severe disease.