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Immune Correlates Analysis of the mRNA-1273 COVID-19 Vaccine Efficacy Trial.
Gilbert, Peter B; Montefiori, David C; McDermott, Adrian; Fong, Youyi; Benkeser, David; 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; Huynh, Chuong; Miller, Jacqueline; El Sahly, Hana M; Baden, Lindsey R; Baron, Mira; De La Cruz, Luis; Gay, Cynthia; Kalams, Spyros; Kelley, Colleen F; Kutner, Mark; Andrasik, Michele P; Kublin, James G; Corey, Lawrence; Neuzil, Kathleen M; Carpp, Lindsay N; Pajon, Rolando; Follmann, Dean; Donis, Ruben O; Koup, Richard A.
Afiliación
  • Gilbert PB; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Montefiori DC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • McDermott A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Fong Y; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Benkeser D; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Deng W; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Zhou H; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Houchens CR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Martins K; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Jayashankar L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Castellino F; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Flach B; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Lin BC; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • O'Connell S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • McDanal C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Eaton A; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Sarzotti-Kelsoe M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Lu Y; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Yu C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Borate B; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • van der Laan LWP; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Hejazi N; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Huynh C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Miller J; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • El Sahly HM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Baden LR; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Baron M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • De La Cruz L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Gay C; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Kalams S; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Kelley CF; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Kutner M; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Andrasik MP; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Kublin JG; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Corey L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Neuzil KM; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Carpp LN; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Pajon R; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Follmann D; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Donis RO; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
  • Koup RA; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA (P.B.G., Y.F., Y.L., C.Y., B.B., L.v.d.L., M.P.A., J.G.K., L.C., L.N.C.); the Vaccine Research Center (A.M., B.F., B.C.L., S.O., R.A.K.) and the Biostatistics Research Branch (D.F.), National Institute of Al
medRxiv ; 2021 Aug 15.
Article en En | MEDLINE | ID: mdl-34401888
ABSTRACT

BACKGROUND:

In the Coronavirus Efficacy (COVE) trial, estimated mRNA-1273 vaccine efficacy against coronavirus disease-19 (COVID-19) was 94%. SARS-CoV-2 antibody measurements were assessed as correlates of COVID-19 risk and as correlates of protection.

METHODS:

Through case-cohort sampling, participants were selected for measurement of four serum antibody markers at Day 1 (first dose), Day 29 (second dose), and Day 57 IgG binding antibodies (bAbs) to Spike, bAbs to Spike receptor-binding domain (RBD), and 50% and 80% inhibitory dilution pseudovirus neutralizing antibody titers calibrated to the WHO International Standard (cID50 and cID80). Participants with no evidence of previous SARS-CoV-2 infection were included. Cox regression assessed in vaccine recipients the association of each Day 29 or 57 serologic marker with COVID-19 through 126 or 100 days of follow-up, respectively, adjusting for risk factors.

RESULTS:

Day 57 Spike IgG, RBD IgG, cID50, and cID80 neutralization levels were each inversely correlated with risk of COVID-19 hazard ratios 0.66 (95% CI 0.50, 0.88; p=0.005); 0.57 (0.40, 0.82; p=0.002); 0.42 (0.27, 0.65; p<0.001); 0.35 (0.20, 0.61; p<0.001) per 10-fold increase in marker level, respectively, multiplicity adjusted P-values 0.003-0.010. Results were similar for Day 29 markers (multiplicity adjusted P-values <0.001-0.003). For vaccine recipients with Day 57 reciprocal cID50 neutralization titers that were undetectable (<2.42), 100, or 1000, respectively, cumulative incidence of COVID-19 through 100 days post Day 57 was 0.030 (0.010, 0.093), 0.0056 (0.0039, 0.0080), and 0.0023 (0.0013, 0.0036). For vaccine recipients at these titer levels, respectively, vaccine efficacy was 50.8% (-51.2, 83.0%), 90.7% (86.7, 93.6%), and 96.1% (94.0, 97.8%). Causal mediation analysis estimated that the proportion of vaccine efficacy mediated through Day 29 cID50 titer was 68.5% (58.5, 78.4%).

CONCLUSIONS:

Binding and neutralizing antibodies correlated with COVID-19 risk and vaccine efficacy and likely have utility in predicting mRNA-1273 vaccine efficacy against COVID-19. TRIAL REGISTRATION NUMBER COVE ClinicalTrials.gov number, NCT04470427.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2021 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: MedRxiv Año: 2021 Tipo del documento: Article