美国Novavax公司Cheryl Keech团队分析了SARS-CoV-2重组刺突蛋白纳米颗粒疫苗临床1-2期试验的结果。2020年9月2日，该研究发表在《新英格兰医学杂志》上。

NVX-CoV2373是一种重组严重急性呼吸综合征冠状病毒2（rSARS-CoV-2）纳米颗粒疫苗，由三聚体全长SARS-CoV-2刺突蛋白和Matrix-M1佐剂组成。

研究组启动了一项随机、安慰剂对照的临床1-2期临床试验，以评估rSARS-CoV-2疫苗在131名参与者中的安全性和免疫原性。在临床1期，疫苗接种包括两次肌肉注射，相隔21天。

将131名参与者随机分组，其中83名接受佐剂疫苗，25名接受无佐剂疫苗，23名接受安慰剂。未发现严重不良事件。在大多数参与者中，反应原性不存在或很轻微，在佐剂中更常见，且持续时间较短（平均≤2天）。1名参与者轻度发烧，持续1天。在大多数参与者中，主动不良事件均为轻度。添加佐剂可增强免疫反应，降低抗原剂量，并诱导T辅助细胞1（Th1）反应。两剂5μg辅助方案诱导的几何平均抗刺突蛋白IgG和中和反应超过了大多数有症状Covid-19患者恢复期血清中的几何平均反应。

接种后第35天，NVX-CoV2373似乎是安全的，且引发的免疫反应超过了Covid-19康复期血清中的水平。Matrix-M1佐剂诱导的CD4⁺ T细胞反应偏向Th1表型。

附：英文原文

Title: Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

Author: Cheryl Keech, M.D., Ph.D.,, Gary Albert, M.S.,, Iksung Cho, M.S.,, Andreana Robertson, M.S.,, Patricia Reed, B.S.,, Susan Neal,, Joyce S. Plested, Ph.D.,, Mingzhu Zhu, Ph.D.,, Shane Cloney-Clark, B.S.,, Haixia Zhou, Ph.D.,, Gale Smith, Ph.D.,, Nita Patel, M.S.,, Matthew B. Frieman, Ph.D.,, Robert E. Haupt, M.S.,, James Logue, B.A.,, Marisa McGrath, B.A.,, Stuart Weston, Ph.D.,, Pedro A. Piedra, M.D.,, Chinar Desai, B.S.,, Kathleen Callahan, M.S.,, Maggie Lewis, M.S.,, Patricia Price-Abbott, M.S.,, Neil Formica, M.B., B.S.,, Vivek Shinde, M.D.,, Louis Fries, M.D.,, Jason D. Lickliter, M.B., B.S., Ph.D.,, Paul Griffin, M.D.,, Bethanie Wilkinson, Ph.D.,, and Gregory M. Glenn, M.D.

Issue&Volume: 2020-09-02

Abstract:

BACKGROUND

NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) nanoparticle vaccine composed of trimeric full-length SARS-CoV-2 spike glycoproteins and Matrix-M1 adjuvant.

METHODS

We initiated a randomized, placebo-controlled, phase 1–2 trial to evaluate the safety and immunogenicity of the rSARS-CoV-2 vaccine (in 5-μg and 25-μg doses, with or without Matrix-M1 adjuvant, and with observers unaware of trial-group assignments) in 131 healthy adults. In phase 1, vaccination comprised two intramuscular injections, 21 days apart. The primary outcomes were reactogenicity; laboratory values (serum chemistry and hematology), according to Food and Drug Administration toxicity scoring, to assess safety; and IgG anti–spike protein response (in enzyme-linked immunosorbent assay [ELISA] units). Secondary outcomes included unsolicited adverse events, wild-type virus neutralization (microneutralization assay), and T-cell responses (cytokine staining). IgG and microneutralization assay results were compared with 32 (IgG) and 29 (neutralization) convalescent serum samples from patients with Covid-19, most of whom were symptomatic. We performed a primary analysis at day 35.

RESULTS

After randomization, 83 participants were assigned to receive the vaccine with adjuvant and 25 without adjuvant, and 23 participants were assigned to receive placebo. No serious adverse events were noted. Reactogenicity was absent or mild in the majority of participants, more common with adjuvant, and of short duration (mean, ≤2 days). One participant had mild fever that lasted 1 day. Unsolicited adverse events were mild in most participants; there were no severe adverse events. The addition of adjuvant resulted in enhanced immune responses, was antigen dose–sparing, and induced a T helper 1 (Th1) response. The two-dose 5-μg adjuvanted regimen induced geometric mean anti-spike IgG (63,160 ELISA units) and neutralization (3906) responses that exceeded geometric mean responses in convalescent serum from mostly symptomatic Covid-19 patients (8344 and 983, respectively).

CONCLUSIONS

At 35 days, NVX-CoV2373 appeared to be safe, and it elicited immune responses that exceeded levels in Covid-19 convalescent serum. The Matrix-M1 adjuvant induced CD4+ T-cell responses that were biased toward a Th1 phenotype.

DOI: 10.1056/NEJMoa2026920

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2026920