Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization.

Published

Journal Article

We investigated the mucosal distribution and neutralization potency of rhesus recombinant versions of the HIV-specific, broadly neutralizing antibody b12 (RhB12) following intravenous administration to lactating rhesus monkeys. IgG and dimeric IgA (dIgA) administration resulted in high plasma concentrations of broadly neutralizing antibody (bnAb), but the monomeric IgA (mIgA) was rapidly cleared from the systemic compartment. Interestingly, differences in the distribution of the RhB12 isoform were observed between the mucosal compartments. The peak concentration of RhB12 IgG was higher than dIgA in saliva, rectal, and vaginal secretions, but the bnAb concentration in milk was one to two logs higher after dIgA administration than with IgG or mIgA infusion. Neutralization was observed in plasma of all animals, but only those infused with RhB12 dIgA showed moderate levels of virus neutralization in milk. Remarkably, virus-specific secretory IgA was detected in mucosal compartments following dIgA administration. The high milk RhB12 dIgA concentration suggests that passive immunization with dIgA could be more effective than IgG to inhibit virus in breast milk.

Full Text

Duke Authors

Cited Authors

  • Fouda, GG; Eudailey, J; Kunz, EL; Amos, JD; Liebl, BE; Himes, J; Boakye-Agyeman, F; Beck, K; Michaels, AJ; Cohen-Wolkowiez, M; Haynes, BF; Reimann, KA; Permar, SR

Published Date

  • January 2017

Published In

Volume / Issue

  • 10 / 1

Start / End Page

  • 228 - 237

PubMed ID

  • 27072605

Pubmed Central ID

  • 27072605

Electronic International Standard Serial Number (EISSN)

  • 1935-3456

Digital Object Identifier (DOI)

  • 10.1038/mi.2016.32

Language

  • eng

Conference Location

  • United States