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Publication Abstract from PubMed

Up to approximately 20% of HIV-infected individuals eventually develop broadly neutralizing antibodies (bnAbs), and many of these antibodies ( approximately 40%) target a region of dense high-mannose glycosylation on gp120 of the HIV envelope protein, known as the "high-mannose patch" (HMP). Thus, there have been numerous attempts to develop glycoconjugate vaccine immunogens that structurally mimic the HMP and might elicit bnAbs targeting this conserved neutralization epitope. Herein, we report on the immunogenicity of glycopeptides, designed by in vitro selection, that bind tightly to anti-HMP antibody 2G12. By analyzing the fine carbohydrate specificity of rabbit antibodies elicited by these immunogens, we found that they differ from some natural human bnAbs, such as 2G12 and PGT128, in that they bind primarily to the core structures within the glycan, rather than to the Manalpha1 --> 2Man termini (2G12) or to the whole glycan (PGT128). Antibody specificity for the glycan core may result from extensive serum mannosidase trimming of the immunogen in the vaccinated animals. This finding has broad implications for vaccine design aiming to target glycan-dependent HIV neutralizing antibodies.

Oligomannose Glycopeptide Conjugates Elicit Antibodies Targeting the Glycan Core Rather than Its Extremities.,Nguyen DN, Xu B, Stanfield RL, Bailey JK, Horiya S, Temme JS, Leon DR, LaBranche CC, Montefiori DC, Costello CE, Wilson IA, Krauss IJ ACS Cent Sci. 2019 Feb 27;5(2):237-249. doi: 10.1021/acscentsci.8b00588. Epub, 2019 Feb 6. PMID:30834312^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.