Antibody Repertoire Analysis of a Zika Virus Infected Patient Revealed that Neutralizing Antibodies are Generated Rapidly After Infection
Qihong Yan1, Xuefeng Niu2, Zhipeng Yao1, Shengnan Zhang1, Hui Lei2, Weiqi Pan2, Linbing Qu1, Ling Chen1,2*
1Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China; 2State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
Zika virus (ZIKV) infection is associated with fetal microcephaly and neurological complications in adults. ZIKV envelope (E) protein mediates viral attachment to the host cells and has been shown to be the major target for neutralizing antibodies. To study antibody response to ZIKV infection, we used single memory B cell PCR to clone 32 monoclonal antibodies (mAbs) that bind to E protein from a patient at 2 months after ZIKV infection. Selected mAbs could neutralize ZIKV in cultured cells and could protect neonatal SCID mice infecting with ZIKV. To have a holistic view of the antibody response, we applied the next generation sequencing to obtain antibody repertoires in PBMC collected on day 14, 64, 181 and 412 after disease onset. Day 14 and day 64 immunoglobulin heavy chain (IgH) repertoires showed significant expansion of many dominant clones with lower degree of diversity, whereas day 181 repertoire recessed to a more quiescent state with few dominant clones but with greater clonal diversity, which is similar to day 412 repertoire. Interestingly, we found the same or similar IgH sequences of 18 out of 32 E-targeted mAbs from day 14 repertoire but not other time points, indicating that these mAbs were generated rapidly after ZIKV infection. Most of these E-targeted mAbs have low somatic mutations. Certain VH genes may preferentially contribute to E-targeted antibodies with only a few somatic mutations. Our study was the first to reveal the dynamic change of antibody response after ZIKV infection through longitudinal analysis of antibody repertoires.
This study was supported by the grant from the Guangzhou Health Care and Cooperative Innovation Major Project (20174020229), and Guangdong Science and Technology Department (No. 2016A020250001).