巴西全球传染病研究Ralf Clemens团队研究了健康成人接种COVID-19蛋白亚单位候选疫苗S-三聚体（SCB-2019）的安全性和免疫原性。2021年1月29日，该研究发表在《柳叶刀》杂志上。

作为加速研发SARS-CoV-2疫苗的一部分，研究组报道了SCB-2019疫苗的剂量发现和佐剂合理性研究。SCB-2019是一种蛋白亚单位候选疫苗，含有稳定的三聚体形式的刺突（S）-蛋白（S-三聚体），并结合两种不同的佐剂。

研究组在澳大利亚的一个专业临床试验中心进行了一项临床1期、随机、双盲、安慰剂对照试验，将健康成人志愿者分为两个年龄组：年轻人（18-54岁）和老年人（55-75岁）。将参与者随机分组，每隔21天分别接种两剂SCB-2019（3μg、9μg或30μg）或安慰剂（0.9%NaCl）。SCB-2019要么不使用佐剂（仅S-三聚体蛋白），要么使用AS03或CpG/明矾佐剂。在每次接种后7天内评估反应性。体液反应通过ELISA检测SCB-2019结合IgG抗体和ACE2竞争性阻断IgG抗体，通过野生型SARS-CoV-2微中和试验检测中和抗体。通过流式细胞术细胞内细胞因子染色检测细胞对聚合S蛋白多肽的反应。

2020年6月19日至9月23日，共有151名志愿者被纳入研究。148名志愿者在第二次给药后至少进行了4周的随访，并纳入本次分析。接种疫苗的耐受性良好，仅有两例发生3级不良事件。大多数局部不良事件为轻度注射部位疼痛，含有AS03佐剂的SCB-2019制剂的局部事件发生率（44–69%）高于含有CpG/明矾佐剂（6–44%）或无佐剂（3–13%）的SCB-2019制剂。

首次给药后，年轻人的全身不良事件发生率（38%）高于老年人（17%），但第二次给药后，两个年龄组的不良事件发生率相差不大（老年人30%，年轻人34%）。不含佐剂的SCB-2019引起最小的免疫反应（第50天发生三次血清转化），但固定剂量SCB-2019添加AS03或CpG/明矾佐剂，在年轻人和老年人中诱导了结合和中和抗体的高滴度和血清转化率。所有AS03剂量组和CpG/Alum 30μg组的滴度均高于COVID-19患者恢复期血清样本的滴度。这两种添加佐剂的SCB-2019制剂均能诱导T-辅助-1偏向性CD4+T细胞应答。

研究结果表明，SCB-2019疫苗由S-三聚体蛋白与AS03或CpG/明矾佐剂组成，可诱导针对SARS-CoV-2的强大体液和细胞免疫应答，具有高病毒中和活性，且患者耐受性良好。

附：英文原文

Title: Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial

Author: Peter Richmond, Lara Hatchuel, Min Dong, Brenda Ma, Branda Hu, Igor Smolenov, Ping Li, Peng Liang, Htay Htay Han, Joshua Liang, Ralf Clemens

Issue&Volume: 2021-01-29

Abstract:

Background

As part of the accelerated development of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we report a dose-finding and adjuvant justification study of SCB-2019, a protein subunit vaccine candidate containing a stabilised trimeric form of the spike (S)-protein (S-Trimer) combined with two different adjuvants.

Methods

Our study is a phase 1, randomised, double-blind placebo-controlled trial at a specialised clinical trials centre in Australia. We enrolled healthy adult volunteers in two age groups: younger adults (aged 18–54 years) and older adults (aged 55–75 years). Participants were randomly allocated either vaccine or placebo using a list prepared by the study funder. Participants were to receive two doses of SCB-2019 (either 3 μg, 9 μg, or 30 μg) or a placebo (0·9% NaCl) 21 days apart. SCB-2019 either had no adjuvant (S-Trimer protein alone) or was adjuvanted with AS03 or CpG/Alum. The assigned treatment was administered in opaque syringes to maintain masking of assignments. Reactogenicity was assessed for 7 days after each vaccination. Humoral responses were measured as SCB-2019 binding IgG antibodies and ACE2-competitive blocking IgG antibodies by ELISA and as neutralising antibodies by wild-type SARS-CoV-2 microneutralisation assay. Cellular responses to pooled S-protein peptides were measured by flow-cytometric intracellular cytokine staining. This trial is registered with ClinicalTrials.gov, NCT04405908; this is an interim analysis and the study is continuing.

Findings

Between June 19 and Sept 23, 2020, 151 volunteers were enrolled; three people withdrew, two for personal reasons and one with an unrelated serious adverse event (pituitary adenoma). 148 participants had at least 4 weeks of follow-up after dose two and were included in this analysis (database lock, Oct 23, 2020). Vaccination was well tolerated, with two grade 3 solicited adverse events (pain in 9 μg AS03-adjuvanted and 9 μg CpG/Alum-adjuvanted groups). Most local adverse events were mild injection-site pain, and local events were more frequent with SCB-2019 formulations containing AS03 adjuvant (44–69%) than with those containing CpG/Alum adjuvant (6–44%) or no adjuvant (3–13%). Systemic adverse events were more frequent in younger adults (38%) than in older adults (17%) after the first dose but increased to similar levels in both age groups after the second dose (30% in older and 34% in younger adults). SCB-2019 with no adjuvant elicited minimal immune responses (three seroconversions by day 50), but SCB-2019 with fixed doses of either AS03 or CpG/Alum adjuvants induced high titres and seroconversion rates of binding and neutralising antibodies in both younger and older adults (anti-SCB-2019 IgG antibody geometric mean titres at day 36 were 1567–4452 with AS03 and 174–2440 with CpG/Alum). Titres in all AS03 dose groups and the CpG/Alum 30 μg group were higher than were those recorded in a panel of convalescent serum samples from patients with COVID-19. Both adjuvanted SCB-2019 formulations elicited T-helper-1-biased CD4+ T-cell responses.

DOI: 10.1016/S0140-6736(21)00241-5

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00241-5/fulltext