Assessing the role of HIV-specific IGA glycosylation on transport and function

The National Institute of Allergy and Infectious Diseases awarded Rush University Medical Center $269,500 on June 5, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to assess the role of HIV-specific IgA glycosylation on transport and function as a foundation for anti-HIV IgA immunotherapy.

The research will characterize glycosylation patterns of bulk IgA isolated from people living with HIV and compare them to non-HIV controls, assessing how these glycosylation profiles influence endothelial transport and correlate with viral load. The project will also clone anti-HIV monomeric IgA and express it in 293 Freestyle cells with knocked-down glycosyltransferases to create glycoengineered IgA, defining optimal glycosylation patterns that maximize endothelial transcytosis. The work builds on prior findings demonstrating that glycosylation patterns of anti-HIV IgG monoclonal antibodies influence their ability to cross the blood-brain barrier and that glycoengineered IgA from colostrum exhibits altered transport properties.

Performance occurs in Chicago, Illinois, with a period of performance from June 5, 2026, through May 31, 2028. This is a Project Grant, a standard assistance type under the program that supports biomedical research and research training in infectious diseases and related areas at public and private nonprofit institutions.

Abstract

The advent of antiretroviral therapy (art) has transformed HIV infection from a fatal disease into a manageable chronic condition. However, people living with HIV continue to experience comorbidities linked to persistent immune activation and inflammation. Unfortunately, there is not a functional vaccine for HIV, and recent efforts to achieve protection through passive immunization with broadly neutralizing anti-HIV IGG antibodies have not been successful. One promising avenue is anti-HIV IGA immunotherapy. Our recent published findings demonstrate that intrarectally applied anti-HIV IGA has an effect on the dissemination of HIV to lymph nodes following intra-rectal challenge. Elucidating the role of biochemical properties, such as glycosylation, on regulating the transport and effector functions of anti-HIV IGA remains poorly understood and requires further investigation. Our previous studies demonstrate that the glycosylation pattern of an anti-HIV IGG monoclonal antibody can influence its ability to disseminate across the blood brain barrier. In addition, we found that glycoengineered IGA isolated from colostrum exhibit altered transport properties. Taken together, these findings support our hypothesis that the glycosylation of IGA influences its cellular transport and can be strategically modified to enhance its transcytosis and function. In aim 1 we will characterize the glycosylation patterns of bulk IGA isolated from people living with HIV and compare them to non-HIV controls. We will then assess how these glycosylation profiles influence endothelial transport and how these changes correlate with viral load. In aim 2 we will clone anti-HIV monomeric IGA and express in 293 freestyle cells that have glycosl- transferases knocked down in order to create glycoengineered IGA. We will define the optimal glycosylation patterns that maximize endothelial transcytosis and antiviral effector functions. We have assembled a team of investigators uniquely equipped to carry out the aims of this grant.