量化单剂量Ad26.COV2.S疫苗效力如何取决于刺突蛋白序列特征。

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

作者信息

Magaret Craig A, Li Li, deCamp Allan C, Rolland Morgane, Juraska Michal, Williamson Brian D, Ludwig James, Molitor Cindy, Benkeser David, Luedtke Alex, Simpkins Brian, Heng Fei, Sun Yanqing, Carpp Lindsay N, Bai Hongjun, Dearlove Bethany L, Giorgi Elena E, Jongeneelen Mandy, Brandenburg Boerries, McCallum Matthew, Bowen John E, Veesler David, Sadoff Jerald, Gray Glenda E, Roels Sanne, Vandebosch An, Stieh Daniel J, Le Gars Mathieu, Vingerhoets Johan, Grinsztejn Beatriz, Goepfert Paul A, de Sousa Leonardo Paiva, Silva Mayara Secco Torres, Casapia Martin, Losso Marcelo H, Little Susan J, Gaur Aditya, Bekker Linda-Gail, Garrett Nigel, Truyers Carla, Van Dromme Ilse, Swann Edith, Marovich Mary A, Follmann Dean, Neuzil Kathleen M, Corey Lawrence, Greninger Alexander L, Roychoudhury Pavitra, Hyrien Ollivier, Gilbert Peter B

机构信息

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

出版信息

Nat Commun. 2024 Mar 11;15(1):2175. doi: 10.1038/s41467-024-46536-w.

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.

在ENSEMBLE随机、安慰剂对照3期试验（NCT04505722）中，估计单剂量Ad26.COV2.S疫苗对中度至重度-危重型COVID-19的疗效（VE）为56%。对484名接种疫苗和1067名接种安慰剂且感染了COVID-19的受试者的SARS-CoV-2刺突序列进行了测定。在这组预先设定的分析中，我们发现，在拉丁美洲，与参考毒株相比，疫苗对拉姆达毒株的VE显著降低，与非拉姆达毒株相比对拉姆达毒株的VE也显著降低[家族性错误率（FWER）p < 0.05]。在16个氨基酸位置上，VE因与疫苗插入序列的残基匹配或不匹配而有所不同（4个FWER p < 0.05；12个q值≤0.20）；对于刺突蛋白、受体结合结构域、N端结构域和S1，VE随与疫苗株序列的物理化学加权汉明距离的增加而显著降低（FWER p < 0.001）；根据9个抗体表位逃逸评分和4个影响NTD中和作用的特征所测量的与疫苗株的距离不同，VE也不同（FWER≤0.05）；并且随对疫苗接种者血清的中和抗性水平降低（p = 0.011）。疫苗对重度-危重型COVID-19的VE在大多数序列特征上是稳定的，但对距离最远的病毒的VE较低。