Shields Adrian M, Faustini Sian E, Hill Harriet J, Al-Taei Saly, Tanner Chloe, Ashford Fiona, Workman Sarita, Moreira Fernando, Verma Nisha, Wagg Hollie, Heritage Gail, Campton Naomi, Stamataki Zania, Drayson Mark T, Klenerman Paul, Thaventhiran James E D, Elkhalifa Shuayb, Goddard Sarah, Johnston Sarah, Huissoon Aarnoud, Bethune Claire, Elcombe Suzanne, Lowe David M, Patel Smita Y, Savic Sinisa, Richter Alex G, Burns Siobhan O
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Department of Clinical Immunology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
Front Immunol. 2022 Jun 2;13:912571. doi: 10.3389/fimmu.2022.912571. eCollection 2022.
Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.
To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.
Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.
Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).
These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency.
原发性和继发性抗体缺陷患者易感染新冠病毒，且在两剂严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗接种方案后反应减弱。已进行第三次初级疫苗接种以增强其体液免疫和细胞免疫。
确定第三次初级SARS-CoV-2免疫接种在异质性抗体缺陷患者队列中的免疫原性。
参与COV-AD研究的参与者在第三次疫苗接种前后进行采样。使用酶联免疫吸附测定（ELISA）、活病毒中和试验和酶联免疫斑点试验（ELISPOT）确定血清学和细胞反应。
按照两剂接种方案，100%的健康对照对SARS-CoV-2疫苗接种产生了血清学反应，然而，38.6%的抗体缺陷个体仍为血清阴性。第三次初级SARS-CoV-2疫苗显著提高了抗刺突糖蛋白抗体血清阳性率，从61.4%提高到76.0%，增加了抗体反应的幅度、中和能力，并使两剂疫苗接种后血清阴性的个体发生血清转化。疫苗诱导的血清学反应对SARS-CoV-2变异株B.1.1.529具有广泛的交叉反应性，然而，血清阳性率和抗体水平仍显著低于健康对照。在最初的两剂疫苗接种方案中，接受阿斯利康ChAdOx1 nCoV-19和辉瑞BioNTech 162b2的个体之间未观察到血清学反应差异。接受异源疫苗作为第三剂的未感染过SARS-CoV-2的参与者在第三次疫苗接种后更有可能产生可检测到的T细胞反应（61.5%对11.1%）。
这些数据支持广泛使用第三次初级免疫接种来增强抗体缺陷个体对SARS-CoV-2的体液免疫。
