Details

Autor(en) / Beteiligte

• Benkeser, David
• Montefiori, David C
• McDermott, Adrian B
• Fong, Youyi
• Janes, Holly E
• Deng, Weiping
• Zhou, Honghong
• Houchens, Christopher R
• Martins, Karen
• Jayashankar, Lakshmi
• Castellino, Flora
• Flach, Britta
• Lin, Bob C
• O'Connell, Sarah
• McDanal, Charlene
• Eaton, Amanda
• Sarzotti-Kelsoe, Marcella
• Lu, Yiwen
• Yu, Chenchen
• Borate, Bhavesh
• van der Laan, Lars W P
• Hejazi, Nima S
• Kenny, Avi
• Carone, Marco
• Williamson, Brian D
• Garver, Jennifer
• Altonen, Erin
• Rudge, Thomas
• Huynh, Chuong
• Miller, Jacqueline
• El Sahly, Hana M
• Baden, Lindsey R
• Frey, Sharon
• Malkin, Elissa
• Spector, Stephen A
• Andrasik, Michele P
• Kublin, James G
• Corey, Lawrence
• Neuzil, Kathleen M
• Carpp, Lindsay N
• Pajon, Rolando
• Follmann, Dean
• Donis, Ruben O
• Koup, Richard A
• Gilbert, Peter B

Titel

Comparing antibody assays as correlates of protection against COVID-19 in the COVE mRNA-1273 vaccine efficacy trial

Ist Teil von

• Science translational medicine, 2023-04, Vol.15 (692), p.eade9078

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 ), and compared and combined markers in multivariable analyses. LV-MN 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.