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Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution...

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Autores principales: Huang, Ying, Hejazi, Nima S., Blette, Bryan, Carpp, Lindsay N., Benkeser, David, Montefiori, David C., McDermott, Adrian B., Fong, Youyi, Janes, Holly E., Deng, Weiping, Zhou, Honghong, Houchens, Christopher R., Martins, Karen, Jayashankar, Lakshmi, Flach, Britta, Lin, Bob C., O’Connell, Sarah, McDanal, Charlene, Eaton, Amanda, Sarzotti-Kelsoe, Marcella, Lu, Yiwen, Yu, Chenchen, Kenny, Avi, Carone, Marco, Huynh, Chuong, Miller, Jacqueline, El Sahly, Hana M., Baden, Lindsey R., Jackson, Lisa A., Campbell, Thomas B., Clark, Jesse, Andrasik, Michele P., Kublin, James G., Corey, Lawrence, Neuzil, Kathleen M., Pajon, Rolando, Follmann, Dean, Donis, Ruben O., Koup, Richard A., Gilbert, Peter B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612023/
https://www.ncbi.nlm.nih.gov/pubmed/37896806
http://dx.doi.org/10.3390/v15102029
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author Huang, Ying
Hejazi, Nima S.
Blette, Bryan
Carpp, Lindsay N.
Benkeser, David
Montefiori, David C.
McDermott, Adrian B.
Fong, Youyi
Janes, Holly E.
Deng, Weiping
Zhou, Honghong
Houchens, Christopher R.
Martins, Karen
Jayashankar, Lakshmi
Flach, Britta
Lin, Bob C.
O’Connell, Sarah
McDanal, Charlene
Eaton, Amanda
Sarzotti-Kelsoe, Marcella
Lu, Yiwen
Yu, Chenchen
Kenny, Avi
Carone, Marco
Huynh, Chuong
Miller, Jacqueline
El Sahly, Hana M.
Baden, Lindsey R.
Jackson, Lisa A.
Campbell, Thomas B.
Clark, Jesse
Andrasik, Michele P.
Kublin, James G.
Corey, Lawrence
Neuzil, Kathleen M.
Pajon, Rolando
Follmann, Dean
Donis, Ruben O.
Koup, Richard A.
Gilbert, Peter B.
author_facet Huang, Ying
Hejazi, Nima S.
Blette, Bryan
Carpp, Lindsay N.
Benkeser, David
Montefiori, David C.
McDermott, Adrian B.
Fong, Youyi
Janes, Holly E.
Deng, Weiping
Zhou, Honghong
Houchens, Christopher R.
Martins, Karen
Jayashankar, Lakshmi
Flach, Britta
Lin, Bob C.
O’Connell, Sarah
McDanal, Charlene
Eaton, Amanda
Sarzotti-Kelsoe, Marcella
Lu, Yiwen
Yu, Chenchen
Kenny, Avi
Carone, Marco
Huynh, Chuong
Miller, Jacqueline
El Sahly, Hana M.
Baden, Lindsey R.
Jackson, Lisa A.
Campbell, Thomas B.
Clark, Jesse
Andrasik, Michele P.
Kublin, James G.
Corey, Lawrence
Neuzil, Kathleen M.
Pajon, Rolando
Follmann, Dean
Donis, Ruben O.
Koup, Richard A.
Gilbert, Peter B.
author_sort Huang, Ying
collection PubMed
description The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.
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spelling pubmed-106120232023-10-29 Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial Huang, Ying Hejazi, Nima S. Blette, Bryan Carpp, Lindsay N. Benkeser, David Montefiori, David C. McDermott, Adrian B. Fong, Youyi Janes, Holly E. Deng, Weiping Zhou, Honghong Houchens, Christopher R. Martins, Karen Jayashankar, Lakshmi Flach, Britta Lin, Bob C. O’Connell, Sarah McDanal, Charlene Eaton, Amanda Sarzotti-Kelsoe, Marcella Lu, Yiwen Yu, Chenchen Kenny, Avi Carone, Marco Huynh, Chuong Miller, Jacqueline El Sahly, Hana M. Baden, Lindsey R. Jackson, Lisa A. Campbell, Thomas B. Clark, Jesse Andrasik, Michele P. Kublin, James G. Corey, Lawrence Neuzil, Kathleen M. Pajon, Rolando Follmann, Dean Donis, Ruben O. Koup, Richard A. Gilbert, Peter B. Viruses Article The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs. MDPI 2023-09-29 /pmc/articles/PMC10612023/ /pubmed/37896806 http://dx.doi.org/10.3390/v15102029 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Ying
Hejazi, Nima S.
Blette, Bryan
Carpp, Lindsay N.
Benkeser, David
Montefiori, David C.
McDermott, Adrian B.
Fong, Youyi
Janes, Holly E.
Deng, Weiping
Zhou, Honghong
Houchens, Christopher R.
Martins, Karen
Jayashankar, Lakshmi
Flach, Britta
Lin, Bob C.
O’Connell, Sarah
McDanal, Charlene
Eaton, Amanda
Sarzotti-Kelsoe, Marcella
Lu, Yiwen
Yu, Chenchen
Kenny, Avi
Carone, Marco
Huynh, Chuong
Miller, Jacqueline
El Sahly, Hana M.
Baden, Lindsey R.
Jackson, Lisa A.
Campbell, Thomas B.
Clark, Jesse
Andrasik, Michele P.
Kublin, James G.
Corey, Lawrence
Neuzil, Kathleen M.
Pajon, Rolando
Follmann, Dean
Donis, Ruben O.
Koup, Richard A.
Gilbert, Peter B.
Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title_full Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title_fullStr Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title_full_unstemmed Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title_short Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial
title_sort stochastic interventional vaccine efficacy and principal surrogate analyses of antibody markers as correlates of protection against symptomatic covid-19 in the cove mrna-1273 trial
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612023/
https://www.ncbi.nlm.nih.gov/pubmed/37896806
http://dx.doi.org/10.3390/v15102029
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