tetano
Editor, Senior Moderator
Nat Commun
. 2024 Nov 12;15(1):9785.
doi: 10.1038/s41467-024-53727-y. Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial
Lindsay N Carpp[SUP] #[/SUP][SUP] 1 [/SUP], Ollivier Hyrien[SUP] #[/SUP][SUP] 1 2 [/SUP], Youyi Fong[SUP] #[/SUP][SUP] 1 2 [/SUP], David Benkeser[SUP] 3 [/SUP], Sanne Roels[SUP] 4 [/SUP], Daniel J Stieh[SUP] 5 6 [/SUP], Ilse Van Dromme[SUP] 4 [/SUP], Griet A Van Roey[SUP] 5 [/SUP], Avi Kenny[SUP] 7 8 9 [/SUP], Ying Huang[SUP] 1 2 7 [/SUP], Marco Carone[SUP] 7 [/SUP], Adrian B McDermott[SUP] 10 11 [/SUP], Christopher R Houchens[SUP] 12 [/SUP], Karen Martins[SUP] 12 [/SUP], Lakshmi Jayashankar[SUP] 12 [/SUP], Flora Castellino[SUP] 12 [/SUP], Obrimpong Amoa-Awua[SUP] 10 [/SUP], Manjula Basappa[SUP] 10 [/SUP], Britta Flach[SUP] 10 [/SUP], Bob C Lin[SUP] 10 [/SUP], Christopher Moore[SUP] 10 [/SUP], Mursal Naisan[SUP] 10 [/SUP], Muhammed Naqvi[SUP] 10 [/SUP], Sandeep Narpala[SUP] 10 [/SUP], Sarah O'Connell[SUP] 10 [/SUP], Allen Mueller[SUP] 10 [/SUP], Leo Serebryannyy[SUP] 10 [/SUP], Mike Castro[SUP] 10 [/SUP], Jennifer Wang[SUP] 10 [/SUP], Christos J Petropoulos[SUP] 13 [/SUP], Alex Luedtke[SUP] 14 [/SUP], Yiwen Lu[SUP] 1 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Michal Juraska[SUP] 1 [/SUP], Nima S Hejazi[SUP] 1 15 [/SUP], Daniel N Wolfe[SUP] 12 [/SUP], Jerald Sadoff[SUP] 5 16 [/SUP], Glenda E Gray[SUP] 17 18 [/SUP], Beatriz Grinsztejn[SUP] 19 [/SUP], Paul A Goepfert[SUP] 20 [/SUP], Linda-Gail Bekker[SUP] 21 22 23 [/SUP], Aditya H Gaur[SUP] 24 [/SUP], Valdilea G Veloso[SUP] 19 [/SUP], April K Randhawa[SUP] 1 [/SUP], Michele P Andrasik[SUP] 1 [/SUP], Jenny Hendriks[SUP] 5 [/SUP], Carla Truyers[SUP] 4 [/SUP], An Vandebosch[SUP] 4 25 [/SUP], Frank Struyf[SUP] 4 26 [/SUP], Hanneke Schuitemaker[SUP] 5 27 [/SUP], Macaya Douoguih[SUP] 5 28 [/SUP], James G Kublin[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 29 [/SUP], Kathleen M Neuzil[SUP] 30 31 [/SUP], Dean Follmann[SUP] 32 [/SUP], Richard A Koup[SUP] 10 [/SUP], Ruben O Donis[SUP] 12 [/SUP], Peter B Gilbert[SUP] 33 34 35 [/SUP]; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; United States Government (USG)/CoVPN Biostatistics Team
Collaborators, Affiliations
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 90[SUP]th[/SUP] 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.
. 2024 Nov 12;15(1):9785.
doi: 10.1038/s41467-024-53727-y. Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial
Lindsay N Carpp[SUP] #[/SUP][SUP] 1 [/SUP], Ollivier Hyrien[SUP] #[/SUP][SUP] 1 2 [/SUP], Youyi Fong[SUP] #[/SUP][SUP] 1 2 [/SUP], David Benkeser[SUP] 3 [/SUP], Sanne Roels[SUP] 4 [/SUP], Daniel J Stieh[SUP] 5 6 [/SUP], Ilse Van Dromme[SUP] 4 [/SUP], Griet A Van Roey[SUP] 5 [/SUP], Avi Kenny[SUP] 7 8 9 [/SUP], Ying Huang[SUP] 1 2 7 [/SUP], Marco Carone[SUP] 7 [/SUP], Adrian B McDermott[SUP] 10 11 [/SUP], Christopher R Houchens[SUP] 12 [/SUP], Karen Martins[SUP] 12 [/SUP], Lakshmi Jayashankar[SUP] 12 [/SUP], Flora Castellino[SUP] 12 [/SUP], Obrimpong Amoa-Awua[SUP] 10 [/SUP], Manjula Basappa[SUP] 10 [/SUP], Britta Flach[SUP] 10 [/SUP], Bob C Lin[SUP] 10 [/SUP], Christopher Moore[SUP] 10 [/SUP], Mursal Naisan[SUP] 10 [/SUP], Muhammed Naqvi[SUP] 10 [/SUP], Sandeep Narpala[SUP] 10 [/SUP], Sarah O'Connell[SUP] 10 [/SUP], Allen Mueller[SUP] 10 [/SUP], Leo Serebryannyy[SUP] 10 [/SUP], Mike Castro[SUP] 10 [/SUP], Jennifer Wang[SUP] 10 [/SUP], Christos J Petropoulos[SUP] 13 [/SUP], Alex Luedtke[SUP] 14 [/SUP], Yiwen Lu[SUP] 1 [/SUP], Chenchen Yu[SUP] 1 [/SUP], Michal Juraska[SUP] 1 [/SUP], Nima S Hejazi[SUP] 1 15 [/SUP], Daniel N Wolfe[SUP] 12 [/SUP], Jerald Sadoff[SUP] 5 16 [/SUP], Glenda E Gray[SUP] 17 18 [/SUP], Beatriz Grinsztejn[SUP] 19 [/SUP], Paul A Goepfert[SUP] 20 [/SUP], Linda-Gail Bekker[SUP] 21 22 23 [/SUP], Aditya H Gaur[SUP] 24 [/SUP], Valdilea G Veloso[SUP] 19 [/SUP], April K Randhawa[SUP] 1 [/SUP], Michele P Andrasik[SUP] 1 [/SUP], Jenny Hendriks[SUP] 5 [/SUP], Carla Truyers[SUP] 4 [/SUP], An Vandebosch[SUP] 4 25 [/SUP], Frank Struyf[SUP] 4 26 [/SUP], Hanneke Schuitemaker[SUP] 5 27 [/SUP], Macaya Douoguih[SUP] 5 28 [/SUP], James G Kublin[SUP] 1 [/SUP], Lawrence Corey[SUP] 1 29 [/SUP], Kathleen M Neuzil[SUP] 30 31 [/SUP], Dean Follmann[SUP] 32 [/SUP], Richard A Koup[SUP] 10 [/SUP], Ruben O Donis[SUP] 12 [/SUP], Peter B Gilbert[SUP] 33 34 35 [/SUP]; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; United States Government (USG)/CoVPN Biostatistics Team
Collaborators, Affiliations
- PMID: 39532861
- PMCID: PMC11557889
- DOI: 10.1038/s41467-024-53727-y
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 90[SUP]th[/SUP] 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.