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Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.

Serum glycan-binding IgG antibodies in HIV-1 infection and during the development of broadly neutralizing responses.
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Scheepers C, Chowdhury S, Wright WS, Campbell CT, Garrett NJ, Abdool Karim Q, Abdool Karim SS, Moore PL, Gildersleeve JC, Morris L,


Scheepers C, Chowdhury S, Wright WS, Campbell CT, Garrett NJ, Abdool Karim Q, Abdool Karim SS, Moore PL, Gildersleeve JC, Morris L, (click to view)

Scheepers C, Chowdhury S, Wright WS, Campbell CT, Garrett NJ, Abdool Karim Q, Abdool Karim SS, Moore PL, Gildersleeve JC, Morris L,

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AIDS (London, England) 31(16) 2199-2209 doi 10.1097/QAD.0000000000001643

Abstract
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.

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