In vivo programming of endogenous antibodies via oral administration of adaptor ligands. Issue 21 (1st November 2017)

• Record Type: Journal Article
• Authors: Nagano, Masanobu; Carrillo, Nancy; Otsubo, Nobumasa; Hakamata, Wataru; Ban, Hitoshi; Fuller, Roberta P.; Bashiruddin, Nasir K.; Barbas, Carlos F.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 21(2017)
• Page Start: 5952
• Page End: 5961
• Publication Date: 2017-11-01
• Subjects: Hapten -- Instant immunization -- Vaccine -- Oral administration -- Immunoconjugate; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.09.010
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Vaccination is a reliable method of prophylaxis and a crucial measure for public health. However, the majority of vaccines cannot be administered orally due to their degradation in the harsh gut environment or inability to cross the GI tract. In this study, we report the first proof-of-concept study of orally producible chemically programmed antibodies via specific conjugation of adaptor ligands to endogenous antibodies, in vivo . Pre-immuniztion with 2, 4-dinitrophenyl (DNP), or the reactive hapten, 1, 3-diketone (DK), or a novel reactive hapten, vinyl sulfone (VS) in mice, followed by oral administration of adaptor ligands composed of the hapten and biotin to the pre-immunized mice resulted in successful in vivo formation of the biotin-hapten-antibody complexes within 2 h. Pharmacokinetic evaluations revealed that apparent serum concentrations of programmed antibodies were up to 144 nM and that the serum half-lives reached up to 34.4 h. These findings show promise for the future development of orally bioavailable drug-hapten-antibody complexes as a strategy to quickly and easily modulate immune targets for aggressive pathogens as well as cancer.