荷兰强生疫苗Macaya Douoguih团队研究了抗Covid-19单剂量Ad26.COV2.S疫苗的安全性和有效性。2021年4月21日，《新英格兰医学杂志》发表了该成果。

Ad26.COV2.S疫苗是一种重组、复制缺陷型人腺病毒26型载体，以融合前稳定的构象编码全长SARS-CoV-2刺突蛋白。

在一项国际性、随机、双盲、安慰剂对照的临床3期试验中，研究组将成年受试者按1：1随机分配，分别接种单剂量Ad26.COV2.S（5×10¹⁰个病毒颗粒）或安慰剂。主要终点是针对SARS-CoV-2检测阴性的符合方案人群参与者中中重度-危重Covid-19的疫苗效力，定义为至少在给药后14天和28天发病。同时对安全性进行了评估。

符合方案的SARS-CoV-2阴性人群中，共有19630名受试者接种Ad26.COV2.S，19691名接种安慰剂。Ad26.COV2.S可有效预防中重度Covid-19，接种后至少14天的有效率为66.9%，接种后至少28天为66.1%。疫苗对危重型Covid-19的疗效更高，接种后至少14天的有效率为76.7%，接种后至少28天为85.4%。

虽然南非91例患者中有86例（94.5%）携带20H/501Y.V2变异株的测序病毒，但疫苗对至少在给药后14天和28天发病的中重度Covid-19的有效性分别为52.0%和64.0%，对危重Covid-19的有效性分别为73.1%和81.7%。Ad26.COV2.S组的反应原性高于安慰剂组，但一般为轻度至中度和暂时性。两组之间严重不良事件的发生率相似。疫苗组中有3例死亡（与Covid-19无关），安慰剂组有16例死亡（5例与Covid-19相关）。

研究结果表明，单剂量的Ad26.COV2.S接种对有症状的Covid-19和无症状的SARS-CoV-2感染有保护作用，对中重度疾病有效，包括住院和死亡。

附：英文原文

Title: Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19

Author: Jerald Sadoff, M.D.,, Glenda Gray, M.B., B.Ch.,, An Vandebosch, Ph.D.,, Vicky Cárdenas, Ph.D.,, Georgi Shukarev, M.D.,, Beatriz Grinsztejn, M.D.,, Paul A. Goepfert, M.D.,, Carla Truyers, Ph.D.,, Hein Fennema, Ph.D.,, Bart Spiessens, Ph.D.,, Kim Offergeld, M.Sc.,, Gert Scheper, Ph.D.,, Kimberly L. Taylor, Ph.D.,, Merlin L. Robb, M.D.,, John Treanor, M.D.,, Dan H. Barouch, M.D.,, Jeffrey Stoddard, M.D.,, Martin F. Ryser, M.D.,, Mary A. Marovich, M.D.,, Kathleen M. Neuzil, M.D.,, Lawrence Corey, M.D.,, Nancy Cauwenberghs, Ph.D.,, Tamzin Tanner, Ph.D.,, Karin Hardt, Ph.D.,, Javier Ruiz-Guiazú, M.D.,, Mathieu Le Gars, Ph.D.,, Hanneke Schuitemaker, Ph.D.,, Johan Van Hoof, M.D.,, Frank Struyf, M.D.,, and Macaya Douoguih, M.D.

Issue&Volume: 2021-04-21

Abstract:

BACKGROUND

The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation.

METHODS

In an international, randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned adult participants in a 1:1 ratio to receive a single dose of Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe–critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among participants in the per-protocol population who had tested negative for SARS-CoV-2. Safety was also assessed.

RESULTS

The per-protocol population included 19,630 SARS-CoV-2–negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe–critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe–critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe–critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe–critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19–related), and 16 in the placebo group (5 were Covid-19–related).

CONCLUSIONS

A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines.

DOI: 10.1056/NEJMoa2101544

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2101544