Rakshit Srabanti, Adiga Vasista, Ahmed Asma, Parthiban Chaitra, Kumar Nirutha Chetan, Dwarkanath Pratibha, Shivalingaiah Sudarshan, Rao Srishti, D'Souza George, Dias Mary, Maguire Thomas J A, Doores Katie, Dasgupta Prokar, Babji Sudhir, Ottenhoff Tom H M, Stuart Kenneth D, De Rosa Stephen, McElrath M Juliana, Vyakarnam Annapurna
Centre for Infectious Disease Research, Indian Institute of Science, Bangalore, India.
Infectious Disease Unit, St. John's Research Institute, Bangalore, India.
Res Sq. 2022 Mar 2:rs.3.rs-1395683. doi: 10.21203/rs.3.rs-1395683/v1.
This study tested if prior BCG revaccination can further boost immune responses subsequently induced by a widely distributed and otherwise efficacious Oxford/AstraZeneca ChAdOx1nCoV-19 vaccine, referred to as COVISHIELD, in India. We compared COVISHIELD induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth and latent tuberculosis negative, after COVISHIELD prime and boost with baseline samples that were collected pre-pandemic and pre-BCG revaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher magnitude of spike-specific Ab and T cell responses, including a greater proportion of high responders; better quality polyfunctional CD4 and CD8 T cells that persisted and a more robust Ab and T cell response to the Delta mutant of SARS-CoV-2 highlighting greater breadth. Mechanistically, BCG adjuvant effects on COVISHIELD induced adaptive responses was associated with more robust innate responses to pathogen-associated-molecular-patterns through TNF-α and IL-1β secretion. This study provides first in-depth analysis of immune responses induced by COVISHIELD in India and highlights the potential of using a cheap and globally available vaccine, BCG, as an adjuvant to enhance heterologous adaptive immune responses induced by COVIDSHIELD and other emerging vaccines.
本研究测试了预先进行卡介苗再接种是否能进一步增强随后由在印度广泛分发且有效的牛津/阿斯利康ChAdOx1 nCoV-19疫苗（称为COVISHIELD）诱导的免疫反应。我们比较了21名卡介苗再接种者（BCG-RV）和13名未进行卡介苗再接种者（BCG-NRV）中COVISHIELD诱导的纵向免疫反应，所有这些人在出生时均接种了卡介苗且潜伏性结核检测呈阴性，在COVISHIELD初免和加强免疫后，与大流行前和卡介苗再接种前采集的基线样本进行比较。与BCG-NRV相比，BCG-RV显示出更高水平的刺突特异性抗体和T细胞反应，包括更高比例的高反应者；持续存在的质量更好的多功能CD4和CD8 T细胞，以及对SARS-CoV-2 Delta变异株更强的抗体和T细胞反应，突出了更广泛的反应广度。从机制上讲，卡介苗对COVISHIELD诱导的适应性反应的佐剂作用与通过TNF-α和IL-1β分泌对病原体相关分子模式产生更强的固有反应有关。本研究首次对COVISHIELD在印度诱导的免疫反应进行了深入分析，并强调了使用廉价且全球可得的疫苗卡介苗作为佐剂来增强由COVIDSHIELD和其他新兴疫苗诱导的异源适应性免疫反应的潜力。
