title: Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization.
abstract: 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.
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Genevieve G
authors.initials: GG
authors.lastname: Fouda
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Joshua
authors.initials: J
authors.lastname: Eudailey
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Erika L
authors.initials: EL
authors.lastname: Kunz
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Amos
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Liebl
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himes
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Felix
authors.initials: F
authors.lastname: Boakye-Agyeman
authors.affiliation: Division of Laboratory Animal Resources, Duke University Medical Center, Durham, NC.
authors.forename: Krista
authors.initials: K
authors.lastname: Beck
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Michaels
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Michael
authors.initials: M
authors.lastname: Cohen-Wolkowiez
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: MassBiologics, University of Massachusetts Medical School, Boston, MA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC.
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000097:blood*; D012634:Bodily Secretions / Q000276:immunology; D001942:Breast Feeding; D019281:Dimerization; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage / Q000097:blood*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D007071:Immunoglobulin A, Secretory / Q000008:administration & dosage / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D008253:Macaca mulatta; D008895:Milk, Human / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology*; D012463:Saliva / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G