Potent Neutralization Ability of a Human Monoclonal Antibody Against Serotype 1 Dengue Virus

• Main Authors: Jiansheng Lu, Rong Wang, Binghui Xia, Yunzhou Yu, Xiaowei Zhou, Zhixin Yang, Peitang Huang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-06-01
• Series: Frontiers in Microbiology
• Subjects: human monoclonal antibody; 1G5; dengue virus serotype 1; envelope protein; antibody-dependent enhancement; antibody neutralization
• Online Access: https://www.frontiersin.org/article/10.3389/fmicb.2018.01214/full

The incidence of dengue virus (DENV) infections has been escalating in tropical and subtropical countries, but there are still no effective therapeutic options. In the present study, a DENV-1-specific human monoclonal antibody (HMAb), 1G5, isolated from single plasma cells obtained from the peripheral blood mononuclear cells of dengue patients was found to have potent neutralization activity against serotype 1 DENV (DENV-1). Its neutralization activity against DENV-2 was not as strong, and it was almost absent for DENV-3 and DENV-4. The results showed that HMAb 1G5 only binds to the envelop protein of intact DENV-1 or the envelop protein under unheated and non-reducing conditions, and that it does not bind to recombinant envelope protein. This could mean that the antibody recognizes a conformational epitope of the envelope protein. Further, the findings showed that HMAb 1G5 potently neutralizes DENV-1 in both the pre- and post-attachment phases of the virus at low concentrations. In vivo studies showed that HMAb 1G5 provides protection from DENV-1 infection in a murine model. In addition, antibody-dependent enhancement that occurs at lower doses of the antibody was completely abrogated by the introduction of Leu-to-Ala mutations (1G5-LALA) or deletion of nine amino acids (1G5-9del) in the Fc region. Therefore, HMAb 1G5 shows promise as a safe and effective agent for prophylactic and therapeutic treatment of DENV-1 infection.