DataSheet_1_Kinetics of the Antibody Response to Boostering With Three Different Vaccines Against SARS-CoV-2.docx

BackgroundHeterologous vaccinations against SARS-CoV-2 with ChAdOx1 nCoV-19 and a second dose of an mRNA-based vaccine have been shown to be more immunogenic than homologous ChAdOx1 nCoV-19. In the current study, we examined the kinetics of the antibody response to the second dose of three different vaccination regimens (homologous ChAdOx1 nCoV-19 vs. ChAdOx1 nCoV-19 + BNT162b2 or mRNA-1273) against SARS-CoV-2 in a longitudinal manner; whether there are differences in latency or amplitude of the early response and which markers are most suitable to detect these responses.
MethodsWe performed assays for anti-S1 IgG and IgA, anti-NCP IgG and a surrogate neutralization assay on serum samples collected from 57 participants on the day of the second vaccination as well as the following seven days.
ResultsAll examined vaccination regimens induced detectable antibody responses within the examined time frame. Both heterologous regimens induced responses earlier and with a higher amplitude than homologous ChAdOx1 nCoV-19. Between the heterologous regimens, amplitudes were somewhat higher for ChAdOx1 nCoV-19 + mRNA-1273. There was no difference in latency between the IgG and IgA responses. Increases in the surrogate neutralization assay were the first changes to be detectable for all regimens and the only significant change seen for homologous ChAdOx1 nCoV-19.
DiscussionBoth examined heterologous vaccination regimens are superior in immunogenicity, including the latency of the response, to homologous ChAdOx1 nCoV-19. While the IgA response has a shorter latency than the IgG response after the first dose, no such difference was found after the second dose, implying that both responses are driven by separate plasma cell populations. Early and steep increases in surrogate neutralization levels suggest that this might be a more sensitive marker for antibody responses after vaccination against SARS-CoV-2 than absolute levels of anti-S1 IgG.

研究背景：现有研究证实，针对新型冠状病毒（SARS-CoV-2）采用ChAdOx1 nCoV-19联合一剂mRNA疫苗（mRNA-based vaccine）的异源接种策略，其免疫原性优于仅使用ChAdOx1 nCoV-19的同源接种策略。本研究采用纵向研究设计，分析了三种不同接种方案（同源ChAdOx1 nCoV-19接种、ChAdOx1 nCoV-19+BNT162b2接种、ChAdOx1 nCoV-19+mRNA-1273接种）中，第二剂接种后针对SARS-CoV-2的抗体应答动力学特征；同时探究了早期应答的潜伏期与幅度是否存在差异，以及何种检测标志物最适于识别此类应答。
研究方法：本研究对57名受试者在第二剂疫苗接种当日及后续7天采集的血清样本开展了检测，包括抗S1 IgG（anti-S1 IgG）、抗S1 IgA（anti-S1 IgA）、抗NCP IgG（anti-NCP IgG）以及替代中和试验（surrogate neutralization assay）。
研究结果：所有受试接种方案在观测时间窗内均可诱导出可检测的抗体应答。两种异源接种方案诱导的抗体应答均早于且幅度高于同源ChAdOx1 nCoV-19接种方案。在两种异源接种方案中，ChAdOx1 nCoV-19+mRNA-1273组合的抗体应答幅度略高。IgG与IgA应答的潜伏期无显著差异。替代中和试验的指标升高是所有接种方案最早可检测到的变化，同时也是同源ChAdOx1 nCoV-19接种方案唯一可观测到的显著变化。
讨论：本研究涉及的两种异源接种方案，在免疫原性（包括应答潜伏期）上均优于同源ChAdOx1 nCoV-19接种方案。尽管首剂接种后IgA应答的潜伏期短于IgG应答，但第二剂接种后未观察到此类差异，这提示两类抗体应答由不同的浆细胞群体介导。替代中和水平的早期快速升高表明，相较于抗S1 IgG的绝对水平，该指标或许是更为灵敏的SARS-CoV-2疫苗接种后抗体应答检测标志物。