Monoclonal Antibodies against Zika Virus NS1 Protein Confer Protection via Fc<b>γ</b>Receptor-Dependent and -Independent Pathways
Lei Yu, Xinglong Liu, Xianmiao Ye, Wan Su, Xiaoyan Zhang, Weiqi Deng, Jia Luo, Mengrong Xiang, Wenjing Guo, Shengnan Zhang, Wei Xü, Qihong Yan, Qian Wang, Yilan Cui, Caixia Wu, Wenjing Guo, Xuefeng Niu, Fuchun Zhang, Chunliang Lei, Linbing Qu, Ling Chen, Liqiang Feng
Abstract
Zika virus (ZIKV) is a mosquito-borne flavivirus that has been linked to congenital microcephaly during recent epidemics. No licensed antiviral drug or vaccine is available. Monoclonal antibodies (MAbs) against the nonstructural protein 1 (NS1) inhibit ZIKV pathogenicity but do not enhance the disease as envelope protein-targeted MAbs do. However, the protection mechanisms are not fully understood. Here, we show that in the presence or absence of Fcγ receptor-bearing effector cells, NS1-targeted human MAbs 3G2 and 4B8 inhibit ZIKV infection. Compared to MAb 4F10 that has no inhibitory effects without effector cells, 3G2 and 4B8 confer better protection in ZIKV-infected neonatal mice. Destroying the Fc-mediated effector function reduces but does not abolish the protection of 3G2 and 4B8, suggesting that they engage both Fcγ receptor-dependent and -independent pathways. The protective efficacy of NS1-targeted MAbs may be associated with their epitope recognition. Our findings will help to develop NS1-based vaccines and therapeutics.