Removal of Anti---Galactosyl Antibodies Elicits Protective Immunity Against Gram-Negative Bacterial Infections

Abstract

Antibody-dependent enhancement (ADE) of infection occurs when nonneutralizing antibodies facilitate the infectivity of pathogens. In humans, antibodies involved in ADE of infections may include those naturally produced against α-galactosyl (αGal) epitopes. Here, we investigate whether the removal of circulating anti-αGal antibodies using a soluble αGal glycopolymer confers protection against Gram-negative bacterial infections. We demonstrate that the intra-corporeal removal of anti-αGal antibodies in an α1,3-galactosyltransferase knockout mouse model is associated with protection against mortality from Gram-negative sepsis after cecal ligation and puncture. Additionally, inhibition of anti-αGal antibodies in vitro from human serum increases the bactericidal effect against E. coli O86:B7 and multi-drug resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. Our results show that protective immunity against Gram-negative bacterial pathogens can be elicited and infectious diseases can be prevented by removing anti-αGal antibodies. The intracorporeal removal of non-neutralizing anti-carbohydrate antibodies with glycopolymers may represent a new approach to providing protection against infectious diseases.