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Master of Public Health

Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features

AUTHORS

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 , . Nature communications. 2024 3 11; 15(1). 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.

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