不同 COVID-19 疫苗平台作为加强针的可互换性：一项模拟真实世界实践的 3 期研究。

Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice.

机构信息

Institute for Global Health, University of Siena, Siena, Italy; Department of Pediatrics, Oxford University, Oxford, UK.

CRIE UNIFESP, Reference Center for Special Immunobiologicals, Federal University of São Paulo, São Paulo, Brazil.

出版信息

Vaccine. 2024 Jul 25;42(19):3989-3998. doi: 10.1016/j.vaccine.2024.05.009. Epub 2024 May 17.

DOI:10.1016/j.vaccine.2024.05.009

PMID:38762360

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11252665/

Abstract

BACKGROUND: The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil. METHODS: In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards. RESULTS: Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles. CONCLUSIONS: Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05812586.

摘要

背景：COVID-19 大流行已经结束，但高度免疫或自然暴露的全球人口仍需要针对新出现的 SARS-CoV-2 变体进行加强接种。我们评估了基于三种不同平台的 COVID-19 疫苗加强剂量在模拟巴西当前常规实践环境中的安全性和免疫原性。

方法：在这项 2023 年 2 月 14 日至 2023 年 6 月 12 日进行的 3 期研究中，我们招募了既往免疫的成年人，以接受三种疫苗之一的额外加强剂量。使用 ELISA IgG 或病毒中和 (VNT) 抗体来测量针对祖先 SARS-CoV-2 和 Omicron BF.7、BQ.1.1.3 和 XBB.1.5.6 亚谱系的免疫原性，并使用日记卡评估安全性/不良反应。

结果：根据其先前加强接种史，有既往 COVID-19 初级免疫史的志愿者分为三组-0（n=26）、1（n=140）或 2（n=606）次加强接种-按 2:1:1 随机分为接受重组蛋白（SCB-2019，Clover）、腺病毒载体（ChAdOx1-S，阿斯利康/Fiocruz）或 mRNA（BNT162b2，辉瑞/Wyeth）。所有组中，接受一剂或两剂加强接种的个体基线抗体滴度较高，无论之前加强接种次数或使用的疫苗如何，针对所有祖先和 Omicron 亚谱系的抗体滴度均增加。所有变体的第 28 天几何平均滴度（GMT）和几何平均倍数升高（GMFR）均高于 BNT162b 高于 SCB-2019 或 ChAdOx1-S，但 BNT162b 组在第 84 天显示出更快的抗体衰减。在每个队列内，每种疫苗对不同的 SARS-CoV-2 株均产生相似的 GMFR。在有 0-2 次既往加强接种的完全初级免疫成年人中，所有疫苗对蛋白、腺病毒载体或 mRNA 疫苗加强接种的耐受性均良好，且对祖先 SARS-CoV-2 和 Omicron 亚谱系均具有免疫原性。

结论：在有 0-2 次既往加强接种的完全初级免疫成年人中，蛋白、腺病毒载体或 mRNA 疫苗加强接种对祖先 SARS-CoV-2 和 Omicron 亚谱系的耐受性和免疫原性均相似。BNT162b 诱导的免疫反应最高，但接种后 3 个月抗体衰减最快。

临床试验注册：ClinicalTrials.gov，标识符 NCT05812586。