EMD-43660
SARS-CoV-2 S RBD (C.37 Lambda variant) plus S309 Fab, local refinement
EMD-43660
Single-particle3.1 Å
Deposition: 08/02/2024Map released: 27/03/2024
Last modified: 08/01/2025
Sample Organism:
Severe acute respiratory syndrome coronavirus 2,
Homo sapiens
Sample: SARS-CoV-2 S C.37 (Lambda variant) plus S309, S2L20, and S2X303 Fabs
Fitted models: 8vyg (Avg. Q-score: 0.395)
Deposition Authors: McCallum M
,
Veesler D ,
Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Sample: SARS-CoV-2 S C.37 (Lambda variant) plus S309, S2L20, and S2X303 Fabs
Fitted models: 8vyg (Avg. Q-score: 0.395)
Deposition Authors: McCallum M
,
Veesler D ,
Seattle Structural Genomics Center for Infectious Disease (SSGCID)
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features.
Magaret CA ,
Li L ,
deCamp AC ,
Rolland M ,
Juraska M ,
Williamson BD ,
Ludwig J ,
Molitor C,
Benkeser D ,
Luedtke A,
Simpkins B ,
Heng F ,
Sun Y ,
Carpp LN ,
Bai H ,
Dearlove BL ,
Giorgi EE,
Jongeneelen M,
Brandenburg B,
McCallum M ,
Bowen JE,
Veesler D ,
Sadoff J ,
Gray GE,
Roels S,
Vandebosch A,
Stieh DJ ,
Le Gars M,
Vingerhoets J ,
Grinsztejn B,
Goepfert PA ,
de Sousa LP ,
Silva MST,
Casapia M ,
Losso MH ,
Little SJ ,
Gaur A,
Bekker LG ,
Garrett N ,
Truyers C,
Van Dromme I,
Swann E,
Marovich MA,
Follmann D ,
Neuzil KM ,
Corey L ,
Greninger AL ,
Roychoudhury P ,
Hyrien O,
Gilbert PB
(2024) Nat Commun , 15 , 2175 - 2175
,
Li L ,
deCamp AC ,
Rolland M ,
Juraska M ,
Williamson BD ,
Ludwig J ,
Molitor C,
Benkeser D ,
Luedtke A,
Simpkins B ,
Heng F ,
Sun Y ,
Carpp LN ,
Bai H ,
Dearlove BL ,
Giorgi EE,
Jongeneelen M,
Brandenburg B,
McCallum M ,
Bowen JE,
Veesler D ,
Sadoff J ,
Gray GE,
Roels S,
Vandebosch A,
Stieh DJ ,
Le Gars M,
Vingerhoets J ,
Grinsztejn B,
Goepfert PA ,
de Sousa LP ,
Silva MST,
Casapia M ,
Losso MH ,
Little SJ ,
Gaur A,
Bekker LG ,
Garrett N ,
Truyers C,
Van Dromme I,
Swann E,
Marovich MA,
Follmann D ,
Neuzil KM ,
Corey L ,
Greninger AL ,
Roychoudhury P ,
Hyrien O,
Gilbert PB
(2024) Nat Commun , 15 , 2175 - 2175
Abstract:
In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.
In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe-critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe-critical COVID-19 was stable across most sequence features but lower against the most distant viruses.