tetano
Editor, Senior Moderator
iScience
. 2025 Sep 29;28(11):113660.
doi: 10.1016/j.isci.2025.113660. eCollection 2025 Nov 21. Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial
Alex Luedtke[SUP] 1 2 3 [/SUP], Youyi Fong[SUP] 2 3 4 [/SUP], Lars van der Laan[SUP] 1 2 [/SUP], Fei Heng[SUP] 5 [/SUP], Ying Huang[SUP] 2 3 4 [/SUP], Yiwen Lu[SUP] 2 [/SUP], Chenchen Yu[SUP] 2 [/SUP], Lindsay N Carpp[SUP] 2 [/SUP], Sanne Roels[SUP] 6 [/SUP], Mathieu Le Gars[SUP] 7 [/SUP], Griet A Van Roey[SUP] 7 [/SUP], Daniel J Stieh[SUP] 7 [/SUP], Ilse Van Dromme[SUP] 6 [/SUP], Avi Kenny[SUP] 8 9 [/SUP], Marco Carone[SUP] 4 [/SUP], Ollivier Hyrien[SUP] 2 3 4 [/SUP], Victor Ayala[SUP] 10 [/SUP], Lakshmi Jayashankar[SUP] 10 [/SUP], Flora Castellino[SUP] 10 [/SUP], Obrimpong Amoa-Awua[SUP] 11 [/SUP], Manjula Basappa[SUP] 11 [/SUP], Britta Flach[SUP] 11 [/SUP], Bob C Lin[SUP] 11 [/SUP], Christopher Moore[SUP] 11 [/SUP], Mursal Naisan[SUP] 11 [/SUP], Muhammed Naqvi[SUP] 11 [/SUP], Sandeep Narpala[SUP] 11 [/SUP], Sarah O'Connell[SUP] 11 [/SUP], Allen Mueller[SUP] 11 [/SUP], Leo Serebryannyy[SUP] 11 [/SUP], Mike Castro[SUP] 11 [/SUP], Jennifer Wang[SUP] 11 [/SUP], Gabrielle Dziubla[SUP] 11 [/SUP], April K Randhawa[SUP] 2 [/SUP], Michele P Andrasik[SUP] 2 [/SUP], Jenny Hendriks[SUP] 7 [/SUP], Carla Truyers[SUP] 6 [/SUP], Frank Struyf[SUP] 6 [/SUP], Hanneke Schuitemaker[SUP] 7 [/SUP], Macaya Douoguih[SUP] 7 [/SUP], James G Kublin[SUP] 2 [/SUP], Lawrence Corey[SUP] 2 12 [/SUP], Kathleen M Neuzil[SUP] 13 [/SUP], Linda-Gail Bekker[SUP] 14 15 16 [/SUP], Nigel Garrett[SUP] 17 18 [/SUP], Sandra W Cardoso[SUP] 19 [/SUP], Patrice DelaFontaine[SUP] 20 21 22 [/SUP], Craig A Magaret[SUP] 2 [/SUP], Johan Vingerhoets[SUP] 6 [/SUP], Martin Casapia[SUP] 23 [/SUP], Marcelo H Losso[SUP] 24 [/SUP], Susan J Little[SUP] 25 [/SUP], Aditya Gaur[SUP] 26 [/SUP], Edith Swann[SUP] 27 [/SUP], Christos J Petropoulos[SUP] 28 [/SUP], Adrian B McDermott[SUP] 11 [/SUP], Jerald Sadoff[SUP] 7 [/SUP], Glenda E Gray[SUP] 29 30 [/SUP], Beatriz Grinsztejn[SUP] 19 [/SUP], Paul A Goepfert[SUP] 31 [/SUP], Dean Follmann[SUP] 32 [/SUP], Pavitra Roychoudhury[SUP] 2 33 [/SUP], Alexander L Greninger[SUP] 2 33 [/SUP], Richard A Koup[SUP] 11 [/SUP], Ruben O Donis[SUP] 10 [/SUP], Peter B Gilbert[SUP] 2 3 4 [/SUP]; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; United States Government (USG)/CoVPN Biostatistics Team
Affiliations
In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.
Keywords: Immune response; Immunology.
. 2025 Sep 29;28(11):113660.
doi: 10.1016/j.isci.2025.113660. eCollection 2025 Nov 21. Immune correlates analysis of antibody responses against SARS-CoV-2 variants in the ENSEMBLE vaccine efficacy trial
Alex Luedtke[SUP] 1 2 3 [/SUP], Youyi Fong[SUP] 2 3 4 [/SUP], Lars van der Laan[SUP] 1 2 [/SUP], Fei Heng[SUP] 5 [/SUP], Ying Huang[SUP] 2 3 4 [/SUP], Yiwen Lu[SUP] 2 [/SUP], Chenchen Yu[SUP] 2 [/SUP], Lindsay N Carpp[SUP] 2 [/SUP], Sanne Roels[SUP] 6 [/SUP], Mathieu Le Gars[SUP] 7 [/SUP], Griet A Van Roey[SUP] 7 [/SUP], Daniel J Stieh[SUP] 7 [/SUP], Ilse Van Dromme[SUP] 6 [/SUP], Avi Kenny[SUP] 8 9 [/SUP], Marco Carone[SUP] 4 [/SUP], Ollivier Hyrien[SUP] 2 3 4 [/SUP], Victor Ayala[SUP] 10 [/SUP], Lakshmi Jayashankar[SUP] 10 [/SUP], Flora Castellino[SUP] 10 [/SUP], Obrimpong Amoa-Awua[SUP] 11 [/SUP], Manjula Basappa[SUP] 11 [/SUP], Britta Flach[SUP] 11 [/SUP], Bob C Lin[SUP] 11 [/SUP], Christopher Moore[SUP] 11 [/SUP], Mursal Naisan[SUP] 11 [/SUP], Muhammed Naqvi[SUP] 11 [/SUP], Sandeep Narpala[SUP] 11 [/SUP], Sarah O'Connell[SUP] 11 [/SUP], Allen Mueller[SUP] 11 [/SUP], Leo Serebryannyy[SUP] 11 [/SUP], Mike Castro[SUP] 11 [/SUP], Jennifer Wang[SUP] 11 [/SUP], Gabrielle Dziubla[SUP] 11 [/SUP], April K Randhawa[SUP] 2 [/SUP], Michele P Andrasik[SUP] 2 [/SUP], Jenny Hendriks[SUP] 7 [/SUP], Carla Truyers[SUP] 6 [/SUP], Frank Struyf[SUP] 6 [/SUP], Hanneke Schuitemaker[SUP] 7 [/SUP], Macaya Douoguih[SUP] 7 [/SUP], James G Kublin[SUP] 2 [/SUP], Lawrence Corey[SUP] 2 12 [/SUP], Kathleen M Neuzil[SUP] 13 [/SUP], Linda-Gail Bekker[SUP] 14 15 16 [/SUP], Nigel Garrett[SUP] 17 18 [/SUP], Sandra W Cardoso[SUP] 19 [/SUP], Patrice DelaFontaine[SUP] 20 21 22 [/SUP], Craig A Magaret[SUP] 2 [/SUP], Johan Vingerhoets[SUP] 6 [/SUP], Martin Casapia[SUP] 23 [/SUP], Marcelo H Losso[SUP] 24 [/SUP], Susan J Little[SUP] 25 [/SUP], Aditya Gaur[SUP] 26 [/SUP], Edith Swann[SUP] 27 [/SUP], Christos J Petropoulos[SUP] 28 [/SUP], Adrian B McDermott[SUP] 11 [/SUP], Jerald Sadoff[SUP] 7 [/SUP], Glenda E Gray[SUP] 29 30 [/SUP], Beatriz Grinsztejn[SUP] 19 [/SUP], Paul A Goepfert[SUP] 31 [/SUP], Dean Follmann[SUP] 32 [/SUP], Pavitra Roychoudhury[SUP] 2 33 [/SUP], Alexander L Greninger[SUP] 2 33 [/SUP], Richard A Koup[SUP] 11 [/SUP], Ruben O Donis[SUP] 10 [/SUP], Peter B Gilbert[SUP] 2 3 4 [/SUP]; Immune Assays Team; Coronavirus Vaccine Prevention Network (CoVPN)/ENSEMBLE Team; United States Government (USG)/CoVPN Biostatistics Team
Affiliations
- PMID: 41210956
- PMCID: PMC12589887
- DOI: 10.1016/j.isci.2025.113660
In Latin American sites of the ENSEMBLE trial of the Ad26.COV2.S vaccine vs. placebo, binding antibodies and neutralizing antibodies measured 4 weeks post-vaccination (∼peak) against circulating lineages (Ancestral, Gamma, Lambda, Mu, Zeta) were assessed as a correlate of risk of, and correlate of protection against, lineage-specific COVID-19. Comparison of lineage-matched controlled vaccine efficacy (VE) curves showed similar relationships across lineages of lineage-specific antibody with VE against lineage-matched COVID-19, supporting a "variant-invariant correlate of protection model" that undergirds immunobridging inferences of efficacy against new variants based on variant-matched neutralizing antibody titers. Lambda departed from this model at undetectable/just-detectable titers: at ∼ peak Reference-specific titers of 2.7 arbitrary units (AU)/mL (just-detectable) and 30 AU/ml, VE against Ancestral COVID-19 was 53.0% (95% CI: 30.7%, 67.9%) and 84.5% (73.6%, 93.0%), respectively; at the same Lambda-specific titers, VE against Lambda COVID-19 was 12.3% (-54.1%, 50.3%) and 91.1% (68.9%, 98.0%). Additional research is needed for Omicron variants.
Keywords: Immune response; Immunology.