Puthanakit Thanyawee, Nantanee Rapisa, Jaru-Ampornpan Peera, Chantasrisawad Napaporn, Sophonphan Jiratchaya, Meepuksom Thutsanun, Jupimai Thidarat, Sodsai Pimpayao, Anugulruengkitt Suvaporn, Hirankarn Nattiya
Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence for Pediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Vaccine X. 2022 Dec;12:100211. doi: 10.1016/j.jvacx.2022.100211. Epub 2022 Aug 29.
Heterologous prime-boost SARS-CoV-2 vaccination is a widely accepted strategy during the COVID-19 pandemic, which generated a superior immune response than homologous vaccination strategy.
To describe immunogenicity of heterologous prime-boost vaccination with inactivated vaccine, CoronaVac, followed by BNT162b2 and 5-month booster dose with BNT162b2 in healthy Thai adolescents.
Adolescents aged 12-18 years were randomized 1:1:1:1 to receive CoronaVac (SV) followed by BNT162b2 (PZ) 30 or 20 µg at either 3- or 6-week interval (SV3w/PZ30µg, SV3w/PZ20µg, SV6w/PZ30µg or SV6w/PZ20µg). During the Omicron-predominant period, participants were offered a BNT162b2 booster dose 30, 15, or 10 µg. Immunogenicity was determined using IgG antibody against spike-receptor-binding domain of wild type(anti-S-RBD IgG) and surrogate virus neutralization test(sVNT) against Delta variant at 14 days and 5 months after the 2 dose. Neutralization tests(sVNT and pseudovirus neutralization test; pVNT) against Omicron strain were tested pre- and 14 days post-booster dose.
In October 2021, 76 adolescents with a median age of 14.3 years (IQR 12.7-16.0) were enrolled: 20 in SV3w/PZ30µg; 17 in SV3w/PZ20µg; 20 in SV6w/PZ30µg; 19 in SV6w/PZ20µg. At day 14, the geometric mean(GM) of anti-S-RBD IgG in SV3w/PZ30µg was 4713 (95 %CI 4127-5382) binding-antibody unit (BAU)/ml, while geometric mean ratio(GMR) was 1.28 (1.09-1.51) in SV6w/PZ30µg. The GMs of sVNT against Delta variants at day 14 among participants in SV3w/PZ30µg and SV6wk/PZ30µg arm were 95.3 % and 99.7 %inhibition, respectively. At 5 months, GMs of sVNT against Delta variants in SV3w/PZ30µg were significantly declined to 47.8 % but remained at 89.0 % inhibition among SV6w/PZ30µg arm. In April 2022, 52 adolescents received a BNT162b2 booster dose. Proportion of participants with sVNT against Omicron strain > 80 %inhibition was significantly increased from 3.8 % pre-booster to 67 % post-booster. Proportion of participants with pVNT ID > 185 was 42 % at 14 days post 2 dose and 88 % post booster, respectively.
Heterologous prime-boost vaccination with CoronaVac followed by BNT162b2 induced high neutralizing titer against SARS-CoV-2 Delta strain. After 5-month interval, booster with BNT162b2 induced high neutralizing titer against Omicron strain.Thai Clinical Trials Registry (thaiclinicaltrials.org): TCTR20210923012.
在新冠疫情期间，异源初免-加强接种新冠病毒疫苗是一种被广泛接受的策略，其产生的免疫反应优于同源接种策略。
描述在健康泰国青少年中，先用灭活疫苗科兴生物（CoronaVac）进行初免，再用BNT162b2进行加强免疫，并在5个月后用BNT162b2进行加强剂量接种的异源初免-加强接种的免疫原性。
将12至18岁的青少年按1:1:1:1随机分组，分别接受科兴生物（SV），随后在3周或6周间隔时接种30μg或20μg的BNT162b2（PZ）（SV3w/PZ30μg、SV3w/PZ20μg、SV6w/PZ30μg或SV6w/PZ20μg）。在以奥密克戎毒株为主的时期，为参与者提供30μg、15μg或10μg的BNT162b2加强剂量。在第2剂接种后的14天和5个月，使用针对野生型刺突受体结合域的IgG抗体（抗S-RBD IgG）和针对德尔塔变体的替代病毒中和试验（sVNT）来确定免疫原性。在加强剂量接种前和接种后14天，对奥密克戎毒株进行中和试验（sVNT和假病毒中和试验；pVNT）。
2021年10月，招募了76名青少年，中位年龄为14.3岁（四分位间距12.7 - 16.0）：SV3w/PZ30μg组20人；SV3w/PZ20μg组17人；SV6w/PZ30μg组20人；SV6w/PZ20μg组19人。在第14天，SV3w/PZ30μg组抗S-RBD IgG的几何平均数（GM）为4713（95%置信区间4127 - 5382）结合抗体单位（BAU）/ml，而SV6w/PZ30μg组的几何平均比值（GMR）为1.28（1.09 - 1.51）。SV3w/PZ30μg组和SV6wk/PZ30μg组参与者在第14天针对德尔塔变体的sVNT几何平均数分别为95.3%和99.7%抑制率。在5个月时，SV3w/PZ30μg组针对德尔塔变体的sVNT几何平均数显著下降至47.8%，但SV6w/PZ30μg组仍保持在89.0%抑制率。2022年4月，52名青少年接受了BNT162b2加强剂量。针对奥密克戎毒株sVNT抑制率>80%的参与者比例从加强前的3.8%显著增加到加强后的67%。在第2剂接种后14天和加强接种后，pVNT ID>185的参与者比例分别为42%和88%。
先用科兴生物进行初免，再用BNT162b2进行加强接种可诱导产生针对新冠病毒德尔塔毒株的高中和滴度。间隔5个月后，用BNT162b2进行加强接种可诱导产生针对奥密克戎毒株的高中和滴度。泰国临床试验注册中心（thaiclinicaltrials.org）：TCTR20210923012 。
