Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization
Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Virus Diseases
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.
DOI of Published Version
Mucosal Immunol. 2017 Jan;10(1):228-237. Epub 2016 Apr 13. Link to article on publisher's site
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. (2017). Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization. Open Access Publications by UMMS Authors. https://doi.org/10.1038/mi.2016.32. Retrieved from https://escholarship.umassmed.edu/oapubs/3082