Author:
Wang Kang,Cao Yunlong,Zhou Yunjiao,Wu Jiajing,Jia Zijing,Hu Yaling,Yisimayi Ayijiang,Fu Wangjun,Wang Lei,Liu Pan,Fan Kaiyue,Chen Ruihong,Wang Lin,Li Jing,Wang Yao,Ge Xiaoqin,Zhang Qianqian,Wu Jianbo,Wang Nan,Wu Wei,Gao Yidan,Miao Jingyun,Jiang Yinan,Qin Lili,Zhu Ling,Huang Weijin,Zhang Yanjun,Zhang Huan,Li Baisheng,Gao Qiang,Xie Xiaoliang Sunney,Wang Youchun,Wang Qiao,Wang Xiangxi
Abstract
AbstractEmergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-resistant and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between “hot” immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines.One sentence summaryA third booster dose of inactivated vaccine produces a highly sifted humoral immune response via a sustained evolution of antibodies capable of effectively neutralizing SARS-CoV-2 variants of concern.
Publisher
Cold Spring Harbor Laboratory