荷兰杨森疫苗与预防公司Hanneke Schuitemaker团队报告了Ad26.COV2.S Covid-19疫苗临床1-2a期试验的中期结果。2021年1月13日，《新英格兰医学杂志》发表了该成果。

目前迫切需要有效的疫苗来遏制正在流行的Covid-19，即SARS-CoV-2感染。候选疫苗Ad26.COV2.S是一种重组、复制抑制型腺病毒血清型26（Ad26）载体，编码全长稳定的SARS-CoV-2刺突蛋白。

在这项多中心、安慰剂对照、临床1-2a期试验中，研究组随机分配18-55岁的健康成人（队列1）和65岁及以上的健康成人（队列3）接种Ad26.COV2.S疫苗，剂量为每毫升5×10¹⁰个病毒颗粒（低剂量）或1×10¹¹个病毒颗粒（高剂量）或安慰剂，采用单剂量或双剂量接种。队列2中收集了比较单剂量方案和双剂量方案的长期数据。主要终点是每种剂量方案的安全性和反应原性。

第1组和第3组的805名参与者接种第一剂疫苗后，以及在第1组接种第二剂疫苗后，最常见的不良事件是疲劳、头痛、肌痛和注射部位疼痛。最常见的全身不良反应是发烧。第3组中系统性不良事件的发生率低于第1组，接种低剂量疫苗的人群中系统性不良事件的发生率低于接种高剂量疫苗的人群。

第二次给药后反应性降低。在第一次接种疫苗后的第29天，90%及以上的接种者检测到针对野生型病毒的中和抗体滴度，几何平均滴度（GMT）为224至354，到第57天达到100%，并且滴度进一步增加，GMT为288至488，无论疫苗的剂量或接种人群的年龄。

滴度至少在第71天仍保持稳定。第二次给药使滴度增加了2.6到2.9倍，GMT为827至1266。刺突结合抗体反应与中和抗体反应相似。第14天，队列1中76%-83%的参与者和队列3中60%-67%的参与者中检测到CD4+T细胞应答，明显偏向1型辅助性T细胞。总体上，CD8+T细胞反应强劲，但队列3中较低。

研究结果表明，Ad26.COV2.S的安全性和免疫原性结果支持该候选疫苗的进一步开发。

附：英文原文

Title: Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine

Author: Jerald Sadoff, M.D.,, Mathieu Le Gars, Ph.D.,, Georgi Shukarev, M.D.,, Dirk Heerwegh, Ph.D.,, Carla Truyers, Ph.D.,, Anne M. de Groot, Ph.D.,, Jeroen Stoop, Ph.D.,, Sarah Tete, Ph.D.,, Wim Van Damme, M.D.,, Isabel Leroux-Roels, M.D.,, Pieter-Jan Berghmans, M.D.,, Murray Kimmel, D.O.,, Pierre Van Damme, M.D.,, Jan de Hoon, M.D.,, William Smith, M.D.,, Kathryn E. Stephenson, M.D.,, Stephen C. De Rosa, M.D.,, Kristen W. Cohen, Ph.D.,, M. Juliana McElrath, M.D.,, Emmanuel Cormier, Ph.D.,, Gert Scheper, Ph.D.,, Dan H. Barouch, M.D.,, Jenny Hendriks, Ph.D.,, Frank Struyf, M.D.,, Macaya Douoguih, M.D.,, Johan Van Hoof, M.D.,, and Hanneke Schuitemaker, Ph.D.

Issue&Volume: 2021-01-13

Abstract:

BACKGROUND

Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.

METHODS

In this multicenter, placebo-controlled, phase 1–2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule.

RESULTS

After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 224 to 354) and reached 100% by day 57 with a further increase in titers (GMT, 288 to 488), regardless of vaccine dose or age group. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 14, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3.

CONCLUSIONS

The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate.

DOI: 10.1056/NEJMoa2034201

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034201