tetano
Editor, Senior Moderator
Sci Transl Med
. 2023 Apr 19;15(692):eade9078.
doi: 10.1126/scitranslmed.ade9078. Epub 2023 Apr 19.
Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial
David Benkeser[SUP] 1 [/SUP], David C Montefiori[SUP] 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP], Youyi Fong[SUP] 4 5 [/SUP], Holly E Janes[SUP] 4 5 [/SUP], Weiping Deng[SUP] 6 [/SUP], Honghong Zhou[SUP] 6 [/SUP], Christopher R Houchens[SUP] 7 [/SUP], Karen Martins[SUP] 7 [/SUP], Lakshmi Jayashankar[SUP] 7 [/SUP], Flora Castellino[SUP] 7 [/SUP], Britta Flach[SUP] 3 [/SUP], Bob C Lin[SUP] 3 [/SUP], Sarah O'Connell[SUP] 3 [/SUP], Charlene McDanal[SUP] 2 [/SUP], Amanda Eaton[SUP] 2 [/SUP], Marcella Sarzotti-Kelsoe[SUP] 2 [/SUP], Yiwen Lu[SUP] 4 [/SUP], Chenchen Yu[SUP] 4 [/SUP], Bhavesh Borate[SUP] 4 [/SUP], Lars W P van der Laan[SUP] 4 [/SUP], Nima S Hejazi[SUP] 4 8 [/SUP], Avi Kenny[SUP] 9 [/SUP], Marco Carone[SUP] 9 [/SUP], Brian D Williamson[SUP] 4 10 [/SUP], Jennifer Garver[SUP] 11 [/SUP], Erin Altonen[SUP] 11 [/SUP], Thomas Rudge[SUP] 11 [/SUP], Chuong Huynh[SUP] 7 [/SUP], Jacqueline Miller[SUP] 6 [/SUP], Hana M El Sahly[SUP] 12 [/SUP], Lindsey R Baden[SUP] 13 [/SUP], Sharon Frey[SUP] 14 [/SUP], Elissa Malkin[SUP] 15 [/SUP], Stephen A Spector[SUP] 16 17 [/SUP], Michele P Andrasik[SUP] 4 [/SUP], James G Kublin[SUP] 4 [/SUP], Lawrence Corey[SUP] 4 18 [/SUP], Kathleen M Neuzil[SUP] 19 [/SUP], Lindsay N Carpp[SUP] 4 [/SUP], Rolando Pajon[SUP] 6 [/SUP], Dean Follmann[SUP] 20 [/SUP], Ruben O Donis[SUP] 7 [/SUP], Richard A Koup[SUP] 3 [/SUP], Peter B Gilbert[SUP] 4 5 9 [/SUP]; Immune Assays; Moderna Inc.; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE); United States Government (USG)/CoVPN Biostatistics Teams
Affiliations
Abstract
The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN[SUB]50[/SUB]), and compared and combined markers in multivariable analyses. LV-MN[SUB]50[/SUB] was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.
. 2023 Apr 19;15(692):eade9078.
doi: 10.1126/scitranslmed.ade9078. Epub 2023 Apr 19.
Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial
David Benkeser[SUP] 1 [/SUP], David C Montefiori[SUP] 2 [/SUP], Adrian B McDermott[SUP] 3 [/SUP], Youyi Fong[SUP] 4 5 [/SUP], Holly E Janes[SUP] 4 5 [/SUP], Weiping Deng[SUP] 6 [/SUP], Honghong Zhou[SUP] 6 [/SUP], Christopher R Houchens[SUP] 7 [/SUP], Karen Martins[SUP] 7 [/SUP], Lakshmi Jayashankar[SUP] 7 [/SUP], Flora Castellino[SUP] 7 [/SUP], Britta Flach[SUP] 3 [/SUP], Bob C Lin[SUP] 3 [/SUP], Sarah O'Connell[SUP] 3 [/SUP], Charlene McDanal[SUP] 2 [/SUP], Amanda Eaton[SUP] 2 [/SUP], Marcella Sarzotti-Kelsoe[SUP] 2 [/SUP], Yiwen Lu[SUP] 4 [/SUP], Chenchen Yu[SUP] 4 [/SUP], Bhavesh Borate[SUP] 4 [/SUP], Lars W P van der Laan[SUP] 4 [/SUP], Nima S Hejazi[SUP] 4 8 [/SUP], Avi Kenny[SUP] 9 [/SUP], Marco Carone[SUP] 9 [/SUP], Brian D Williamson[SUP] 4 10 [/SUP], Jennifer Garver[SUP] 11 [/SUP], Erin Altonen[SUP] 11 [/SUP], Thomas Rudge[SUP] 11 [/SUP], Chuong Huynh[SUP] 7 [/SUP], Jacqueline Miller[SUP] 6 [/SUP], Hana M El Sahly[SUP] 12 [/SUP], Lindsey R Baden[SUP] 13 [/SUP], Sharon Frey[SUP] 14 [/SUP], Elissa Malkin[SUP] 15 [/SUP], Stephen A Spector[SUP] 16 17 [/SUP], Michele P Andrasik[SUP] 4 [/SUP], James G Kublin[SUP] 4 [/SUP], Lawrence Corey[SUP] 4 18 [/SUP], Kathleen M Neuzil[SUP] 19 [/SUP], Lindsay N Carpp[SUP] 4 [/SUP], Rolando Pajon[SUP] 6 [/SUP], Dean Follmann[SUP] 20 [/SUP], Ruben O Donis[SUP] 7 [/SUP], Richard A Koup[SUP] 3 [/SUP], Peter B Gilbert[SUP] 4 5 9 [/SUP]; Immune Assays; Moderna Inc.; Coronavirus Vaccine Prevention Network (CoVPN)/Coronavirus Efficacy (COVE); United States Government (USG)/CoVPN Biostatistics Teams
Affiliations
- PMID: 37075127
- DOI: 10.1126/scitranslmed.ade9078
Abstract
The best assay or marker to define mRNA-1273 vaccine-induced antibodies as a correlate of protection (CoP) is unclear. In the COVE trial, participants received two doses of the mRNA-1273 COVID-19 vaccine or placebo. We previously assessed IgG binding antibodies to the spike protein (spike IgG) or receptor binding domain (RBD IgG) and pseudovirus neutralizing antibody 50 or 80% inhibitory dilution titer measured on day 29 or day 57, as correlates of risk (CoRs) and CoPs against symptomatic COVID-19 over 4 months after dose. Here, we assessed a new marker, live virus 50% microneutralization titer (LV-MN[SUB]50[/SUB]), and compared and combined markers in multivariable analyses. LV-MN[SUB]50[/SUB] was an inverse CoR, with a hazard ratio of 0.39 (95% confidence interval, 0.19 to 0.83) at day 29 and 0.51 (95% confidence interval, 0.25 to 1.04) at day 57 per 10-fold increase. In multivariable analyses, pseudovirus neutralization titers and anti-spike binding antibodies performed best as CoRs; combining antibody markers did not improve correlates. Pseudovirus neutralization titer was the strongest independent correlate in a multivariable model. Overall, these results supported pseudovirus neutralizing and binding antibody assays as CoRs and CoPs, with the live virus assay as a weaker correlate in this sample set. Day 29 markers performed as well as day 57 markers as CoPs, which could accelerate immunogenicity and immunobridging studies.