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Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses
Cathrine Scheepers1, Sudipa Chowdhury, W Shea Wright
1aCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa bSchool of Pathology, University of the Witwatersrand, Johannesburg, South Africa cChemical Glycobiology Section of the Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland, USA dCentre for the AIDS Programme of Research in South Africa (CAPRISA), KwaZulu-Natal, South Africa eDepartment of Epidemiology, Columbia University, New York City, New York, USA.
Background:
The HIV-1 envelope is covered with glycans that provide structural integrity and protect conserved regions from host antibody responses. However, these glycans are often the target of broadly neutralizing antibodies (bNAbs) that emerge in some HIV-infected individuals. We aimed to determine whether antiglycan IgG antibodies are a general response to HIV-1 infection or specific to individuals who develop bNAbs.
Methods:
IgG binding to glycans was assessed using arrays that contained 245 unique components including N-linked carbohydrates, glycolipids, and Tn-peptides. Sera from 20 HIV-negative and 27 HIV-positive women (including 12 individuals who developed bNAbs) were profiled longitudinally. HIV-1 gp120 proteins were used to compete for binding to the array.
Results:
Antiglycan IgG antibodies fluctuated over a 3-year period, irrespective of HIV infection. However, HIV-positive individuals had elevated binding to 40 components on the array that included Man8, Man9, Tn-peptides, heat shock protein, and glycolipids. Competition experiments confirmed that a proportion of these glycan-binding IgG antibodies were HIV-1-specific, some of which were higher in individuals who developed bNAbs.
Conclusions:
HIV-1 infection is associated with elevated levels of IgG antibodies to specific glycans. Furthermore, some antiglycan IgG antibodies were more abundant in individuals with bNAbs, suggesting a unique phenotype that may be informative for HIV vaccine design.
