Occluding the Mannose Moieties on Human Immunodeficiency Virus Type 1 gp120 with Griffithsin Improves the Antibody Responses to Both Proteins in Mice

Department of Microbiology and Immunology, Weill Cornell Medical College, New York, New York 10021, USA.
AIDS research and human retroviruses (Impact Factor: 2.33). 07/2011; 28(2):206-14. DOI: 10.1089/aid.2011.0101
Source: PubMed


To assess the influence of mannosylated glycans on the immunogenicity of human immunodeficiency virus type 1 (HIV-1) Env proteins, we immunized mice with monomeric gp120 in the presence and absence of the mannose-binding protein, griffithsin (GRFT). For comparison, other groups of mice received the nonglycosylated HIV-1 Gag protein, with and without GRFT. Coimmunization with GRFT increased the anti-gp120 IgG reactivity significantly, but had no effect on the anti-Gag response. We also investigated the IgG response to GRFT and found that gp120, but not Gag, enhanced its immunogenicity. For both proteins, IgG1 antibodies dominated the IgG response, with IgG2b as the next most prevalent subclass. We conclude that gp120-GRFT complexes are more immunogenic than the free proteins, for both components, and that occluding the mannose moieties on monomeric gp120 can improve the humoral immune response to this protein.

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Available from: Per Johan Klasse, Feb 02, 2016
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    • "The Ab response against Env requires multiple booster vaccinations and wanes quickly with a half-life of 30–60 days [32], [33]. One explanation is that N-linked oligomannose glycans on Env actively suppress immune cell functioning [34]–[37]. Indeed, vaccination studies in mice showed that de-mannosylated gp120 was more immunogenic than unmodified gp120 [38]. Taken together, a variety of Env properties may reduce its immunogenicity. "
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    • "HIV-1 gp120 can bind to many immune-system molecules, including CD4, CCR5, CXCR4 and MCLRs, thereby potentially interfering with key components of the immune system [16]. Suppressive effects of gp120 on diverse functions of a number of immune cells, including plasmacytoid DCs and monocyte-derived DCs, have been observed in vitro [17]–[19], and gp120 can also suppress immune responses in vivo [20]–[22], [24]. Given that Env vaccines are often delivered in considerable amounts (several hundred µg) to local sites, it is possible that the receptor-binding properties of these proteins could impair their immunogenicity [16]. "
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