Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses
Abstract
Sequential dengue virus (DENV) infections often generate neutralizing antibodies against all four DENV serotypes and sometimes, Zika virus. Characterizing cross-flavivirus broadly neutralizing antibody (bnAb) responses can inform countermeasures that avoid enhancement of infection associated with non-neutralizing antibodies. Here, we used single cell transcriptomics to mine the bnAb repertoire following repeated DENV infections. We identified several new bnAbs with comparable or superior breadth and potency to known bnAbs, and with distinct recognition determinants. Unlike all known flavivirus bnAbs, which are IgG1, one newly identified cross-flavivirus bnAb (F25.S02) was derived from IgA1. Both IgG1 and IgA1 versions of F25.S02 and known bnAbs displayed neutralizing activity, but only IgG1 enhanced infection in monocytes expressing IgG and IgA Fc receptors. Moreover, IgG-mediated enhancement of infection was inhibited by IgA1 versions of bnAbs. We demonstrate a role for IgA in flavivirus infection and immunity with implications for vaccine and therapeutic strategies.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 09, 2023
- Source ID
- 10.1371/journal.ppat.1011722
Entities
People
- Ana M. Sanz
- Benjamin J Doranz
- Caroline Kikawa
- Catiana H. Cartwright-acar
- David E. Rebellon-sanchez
- Duncan K. Ralph
- Edgar Davidson
- Fernando Rosso
- Frederick A. Matsen Iv
- Jay Lubow
- Laura Belmont
- Leslie Goo
- Lisa M. Levoir
- Maya Contreras
- Shirit Einav
- Shruthi Kannan
- Veronica Duran
Organizations
- Chan Zuckerberg Biohub
- Congressionally Directed Medical Research Programs
- Dr. Ralph and Marian Falk Medical Research Trust
- Fred Hutchinson Cancer Center
- Howard Hughes Medical Institute
- National Institutes of Health