Ascaso-Del-Rio Ana, García-Pérez Javier, Pérez-Olmeda Mayte, Arana-Arri Eunate, Vergara Itziar, Pérez-Ingidua Carla, Bermejo Mercedes, Castillo de la Osa María, Imaz-Ayo Natale, Riaño Fernández Ioana, Astasio González Oliver, Díez-Fuertes Francisco, Meijide Susana, Arrizabalaga Julio, Hernández Gutiérrez Lourdes, de la Torre-Tarazona Humberto Erick, Mariano Lázaro Alberto, Vargas-Castrillón Emilio, Alcamí José, Portolés Antonio
Clinical Pharmacology Department, Hospital Clínico San Carlos, IdISSC, C/ Prof Martín Lagos s/n, 28040 Madrid, Spain.
Instituto de Investigación Sanitaria del hospital Clínico San Carlos.
EClinicalMedicine. 2022 Jul 1;51:101542. doi: 10.1016/j.eclinm.2022.101542. eCollection 2022 Sep.
There is no evidence to date on immunogenic response among individuals who participated in clinical trials of COVID-19 experimental vaccines redirected to standard national vaccination regimens.
This multicentre, prospective controlled cohort study included subjects who received a COVID-19 experimental vaccine (CVnCoV)(test group, TG) - and unvaccinated subjects (control group, CG), selected among individuals to be vaccinated according to the Spanish vaccination program. All study subjects received BNT162b2 as a standard national vaccination schedule, except 8 (from CG) who received mRNA-1273 and were excluded from immunogenicity analyses. Anti-RBD antibodies level and neutralising titres (NT50) against G614, Beta, Mu, Delta and Omicron variants were analysed. Reactogenicity was also assessed.
130 participants (TG:92; CG:38) completed standard vaccination. In TG, median (IQR) of anti-RBD antibodies after first BNT162b2 dose were 10740·0 BAU/mL (4466·0-12500) compared to 29·8 BAU/mL (14·5-47·8) in CG ( <0·0001). Median NT50 (IQR) of G614 was 2674·0 (1865·0-3997·0) in TG and 63·0 (16·0-123·1) in CG ( <0·0001). After second BNT162b2 dose, anti-RBD levels increased to ≥12500 BAU/mL (11625·0-12500) in TG compared to 1859·0 BAU/mL (915·4-3820·0) in CG ( <0·0001). NT50 was 2626·5 (1756·0-5472·0) and 850·4 (525·1-1608·0), respectively ( <0·0001). Variant-specific (Beta, Mu, Omicron) response was also assessed. Most frequent adverse reactions were headache, myalgia, and local pain. No severe AEs were reported.
Heterologous BNT162b2 as third and fourth doses in previously suboptimal immunized individuals elicit stronger immune response than that obtained with two doses of BNT162b2. This apparent benefit was also observed in variant-specific response. No safety concerns arose.
Partly funded by the Institute of Health Carlos-III and COVID-19 Fund, co-financed by the European Regional Development Fund (FEDER) "A way to make Europe".
迄今为止，尚无证据表明参与新冠病毒实验性疫苗临床试验且转而采用标准国家疫苗接种方案的个体的免疫原性反应情况。
这项多中心、前瞻性对照队列研究纳入了根据西班牙疫苗接种计划在待接种个体中选取的接种新冠病毒实验性疫苗（CVnCoV）的受试者（试验组，TG）和未接种疫苗的受试者（对照组，CG）。除8名（来自CG）接种了mRNA - 1273且被排除在免疫原性分析之外的受试者外，所有研究受试者均按照标准国家疫苗接种计划接种BNT162b2。分析了抗受体结合域（RBD）抗体水平以及针对G614、贝塔、缪、德尔塔和奥密克戎变体的中和滴度（NT50）。还评估了反应原性。
130名参与者（TG：92名；CG：38名）完成了标准疫苗接种。在试验组中，首次接种BNT162b2剂量后抗RBD抗体的中位数（四分位间距）为10740.0 BAU/mL（4466.0 - 12500），而对照组为29.8 BAU/mL（14.5 - 47.8）（<0.0001）。试验组中G614的NT50中位数（四分位间距）为2674.0（1865.0 - 3997.0），对照组为63.0（16.0 - 123.1）（<0.0001）。第二次接种BNT162b2剂量后，试验组抗RBD水平升至≥12500 BAU/mL（11625.0 - 12500），而对照组为1859.0 BAU/mL（915.4 - 3820.0）（<0.0001）。NT50分别为2626.5（1756.0 - 5472.0）和850.4（525.1 - 1608.0）（<0.0001）。还评估了变体特异性（贝塔、缪、奥密克戎）反应。最常见的不良反应为头痛、肌痛和局部疼痛。未报告严重不良事件。
在先前免疫效果欠佳的个体中，异源接种BNT162b2作为第三剂和第四剂引发的免疫反应比两剂BNT162b2更强。在变体特异性反应中也观察到了这种明显的益处。未出现安全问题。
部分由卡洛斯三世卫生研究所和新冠病毒基金资助，由欧洲区域发展基金（FEDER）“打造欧洲的途径”共同资助。
