■在并行组中,国际,3期研究(ClinicalTrials.govNCT04762680),我们评估了含有AS03佐剂(CoV2preSdTM-AS03)的原型(D614)和Beta(B.1.351)变体重组刺突蛋白加强疫苗。
■成人,以前用mRNA(BNT162b2,mRNA-1273),腺病毒载体(Ad26。CoV2。S,ChAdOx1nCoV-19)或蛋白质(CoV2preSdTM-AS03[单价D614;MV(D614)])疫苗于2021年7月29日至2022年2月22日注册。参与者按年龄(18-55岁和≥56岁)进行分层,并接受以下CoV2preSdTM-AS03增强制剂之一:MV(D614)(n=1285),MV(B.1.351)(n=707)或二价D614+B.1.351(BiV;n=625)。在SARS-CoV-2快速诊断测试中测试为阴性的未接种疫苗的成年人(对照组,n=479)接受了两个主要剂量,相隔21天,MV(D614)。在加强后14天(第[D]15天),在18-55岁的BNT162b2引发的参与者中,使用经过验证的假病毒(慢病毒)中和(PsVN)测定法评估了抗D614G和抗B.1.351抗体,并与那些预加强(D1)和18-55岁对照的D36(主要免疫原性终点)进行了比较。还评估了对OmicronBA.1、BA.2和BA4/5亚变体的PsVN滴度。在12个月的随访期内评估安全性。计划的中期分析在最后一次疫苗接种后长达14天的免疫原性和在5个月的中位持续时间内的安全性。
■所有三种增强剂都引发了强烈的抗D614G或-B.1.351PsVNmRNA反应,腺病毒载体和蛋白质疫苗启动组。在BNT162b2-primed成年人(18-55岁)中,个体加强后与加强前滴度比率的几何平均值(95%置信区间[CI])为:对于MV(D614),23.37(18.58-29.38)(反D614G);对于MV(B.1.351),35.41(26.71-46.95)(反B.1.351);对于BiV,14.39(11.39-18.28)(抗D614G)和34.18(25.84-45.22(抗B.1.351)。对照中GMT比率(98.3%CI)与初次疫苗接种后GMT,为:MV(D614)助推器,2.16(1.69;2.75)[反D614G];对于MV(B.1.351),1.96(1.54;2.50)[反B.1.351];对于BiV,2.34(1.84;2.96)[反D614G]和1.39(1.09;1.77)[反B.1.351]。所有加强制剂都引发了针对OmicronBA.2的交叉中和抗体(跨引发疫苗亚组),OmicronBA.1(BNT162b2启动参与者)和OmicronBA.4/5(BNT162b2启动参与者和MVD614启动参与者)。在年龄≥56岁的参与者中观察到类似的抗体应答模式。在所有加强组中,反应性往往是短暂的和轻度至中度的严重程度。没有发现安全问题。
■CoV2preSdTM-AS03增强剂显示出可接受的安全性,并引发针对多种变体的强大中和抗体,不管启动疫苗。
■赛诺菲和生物医学高级研究与发展局(BARDA)。
UNASSIGNED: In a parallel-group, international, phase 3
study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and
Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03).
UNASSIGNED: Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18-55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18-55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18-55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety.
UNASSIGNED: All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18-55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58-29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71-46.95) (anti-B.1.351); and for BiV, 14.39 (11.39-18.28) (anti-D614G) and 34.18 (25.84-45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified.
UNASSIGNED: CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine.
UNASSIGNED: Sanofi and Biomedical Advanced Research and Development Authority (BARDA).