Siriraj Institute of Clinical Research, Bangkok, Thailand.
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Front Immunol. 2023 Jan 17;13:1080791. doi: 10.3389/fimmu.2022.1080791. eCollection 2022.
This phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19.
Participants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools.
Immunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P < 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P < 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts.
We concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks.
本 I 期研究旨在探索 COVID-19 加速、Q7 分数、皮内接种方案的免疫原性和反应原性。
本研究纳入了 60 名年龄在 18-60 岁之间、未感染 SARS-CoV-2 或接种过疫苗的参与者，将其随机分为四组，每组接受两剂、两针、间隔七天的同源或异源加速皮内接种方案：（1）BNT162b2-BNT162b2（n=20）；（2）ChAdOx1-BNT162b2（n=20）；（3）CoronaVac-ChAdOx1（n=10）；和（4）ChAdOx1-ChAdOx1（n=10）。CoronaVac 和 ChAdOx1 为其肌肉内标准剂量的 20%（分别为每针 0.1 毫升和 0.05 毫升），而 BNT162b2 为 17%。通过测量针对原始 SARS-CoV-2 刺突蛋白受体结合域（RBD-IgG）的 IgG 反应和假病毒中和试验（PVNT50）来评估体液免疫应答。使用 ELISpot 测量针对原始蛋白池的细胞免疫应答。
第二剂后两周，方案（2）的免疫原性最高，其次是方案（1）、（4）和（3）（抗 RBD-IgG 方面 P<0.001，PVNT50 方面 P=0.01）。与各自的肌肉内标准方案相比，每组的抗 RBD IgG 均显著降低（方案（1）至（4）分别为 5.4、3.6、11.6 和 2.0 倍）（每个 P<0.001）。针对原始株的 PVNT50 血清转化率分别为方案（1）至（4）的 75%、90%、57%和 37%。接种疫苗后，所有参与者均对 S 蛋白产生了 ELISpot 反应。各队列报告的不良反应均为轻度或中度。
我们得出结论，BNT162b2 和 ChAdOx1 的加速、分数、异源或同源皮内接种方案具有良好的耐受性，可快速引发针对 SARS-CoV-2 的免疫原性，并可能有助于控制未来的疫情爆发。
