8ef1

Publication Abstract from PubMed

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.,Sankhala RS, Dussupt V, Donofrio G, Gromowski GD, De La Barrera RA, Larocca RA, Mendez-Rivera L, Lee A, Choe M, Zaky W, Mantus G, Jensen JL, Chen WH, Gohain N, Bai H, McCracken MK, Mason RD, Leggat D, Slike BM, Tran U, Jian N, Abbink P, Peterson R, Mendes EA, Freitas de Oliveira Franca R, Calvet GA, Bispo de Filippis AM, McDermott A, Roederer M, Hernandez M, Albertus A, Davidson E, Doranz BJ, Rolland M, Robb ML, Lynch RM, Barouch DH, Jarman RG, Thomas SJ, Modjarrad K, Michael NL, Krebs SJ, Joyce MG Cell Rep. 2023 Aug 29;42(8):112942. doi: 10.1016/j.celrep.2023.112942. Epub 2023 , Aug 9. PMID:37561630^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.