Stochastic interventional approach to assessing immune correlates of protection: Application to the COVE messenger RNA-1273 vaccine trial.
Correlate of protection
Neutralizing antibody titer
Phase III trial
Stochastic interventional vaccine efficacy analysis
Journal
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
13
07
2023
revised:
30
08
2023
accepted:
17
09
2023
medline:
4
12
2023
pubmed:
12
10
2023
entrez:
11
10
2023
Statut:
ppublish
Résumé
Stochastic interventional vaccine efficacy (SVE) analysis is a new approach to correlate of protection (CoP) analysis of a phase III trial that estimates how vaccine efficacy (VE) would change under hypothetical shifts of an immune marker. We applied nonparametric SVE methodology to the COVE trial of messenger RNA-1273 vs placebo to evaluate post-dose 2 pseudovirus neutralizing antibody (nAb) titer against the D614G strain as a CoP against COVID-19. Secondly, we evaluated the ability of these results to predict VE against variants based on shifts of geometric mean titers to variants vs D614G. Prediction accuracy was evaluated by 13 validation studies, including 12 test-negative designs. SVE analysis of COVE supported post-dose 2 D614G titer as a CoP: estimated VE ranged from 66.9% (95% confidence interval: 36.2, 82.8%) to 99.3% (99.1, 99.4%) at 10-fold decreased or increased titer shifts, respectively. The SVE estimates only weakly predicted variant-specific VE estimates (concordance correlation coefficient 0.062 for post 2-dose VE). SVE analysis of COVE supports nAb titer as a CoP for messenger RNA vaccines. Predicting variant-specific VE proved difficult due to many limitations. Greater anti-Omicron titers may be needed for high-level protection against Omicron vs anti-D614G titers needed for high-level protection against pre-Omicron COVID-19.
Sections du résumé
BACKGROUND
BACKGROUND
Stochastic interventional vaccine efficacy (SVE) analysis is a new approach to correlate of protection (CoP) analysis of a phase III trial that estimates how vaccine efficacy (VE) would change under hypothetical shifts of an immune marker.
METHODS
METHODS
We applied nonparametric SVE methodology to the COVE trial of messenger RNA-1273 vs placebo to evaluate post-dose 2 pseudovirus neutralizing antibody (nAb) titer against the D614G strain as a CoP against COVID-19. Secondly, we evaluated the ability of these results to predict VE against variants based on shifts of geometric mean titers to variants vs D614G. Prediction accuracy was evaluated by 13 validation studies, including 12 test-negative designs.
RESULTS
RESULTS
SVE analysis of COVE supported post-dose 2 D614G titer as a CoP: estimated VE ranged from 66.9% (95% confidence interval: 36.2, 82.8%) to 99.3% (99.1, 99.4%) at 10-fold decreased or increased titer shifts, respectively. The SVE estimates only weakly predicted variant-specific VE estimates (concordance correlation coefficient 0.062 for post 2-dose VE).
CONCLUSION
CONCLUSIONS
SVE analysis of COVE supports nAb titer as a CoP for messenger RNA vaccines. Predicting variant-specific VE proved difficult due to many limitations. Greater anti-Omicron titers may be needed for high-level protection against Omicron vs anti-D614G titers needed for high-level protection against pre-Omicron COVID-19.
Identifiants
pubmed: 37820782
pii: S1201-9712(23)00727-0
doi: 10.1016/j.ijid.2023.09.012
pii:
doi:
Substances chimiques
Antibodies, Neutralizing
0
RNA, Messenger
0
Vaccines
0
Antibodies, Viral
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
28-39Subventions
Organisme : NIAID NIH HHS
ID : UM1 AI068635
Pays : United States
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declarations of competing interest WD, HZ, and BL are employed by Moderna, Inc. and have stock and/or stock options in Moderna, Inc. DCM's laboratory receives funding from Moderna, Inc. to perform neutralizing antibody assays on serum samples from their clinical studies of COVID-19 vaccines.