Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo.

TitleEnzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo.
Publication TypeJournal Article
Year of Publication2009
AuthorsBanerjee K, Andjelic S, Klasse PJohan, Kang Y, Sanders RW, Michael E, Durso RJ, Ketas TJ, Olson WC, Moore JP
Date Published2009 Jun 20
KeywordsAdjuvants, Immunologic, AIDS Vaccines, Animals, Antibodies, Monoclonal, CHO Cells, Cricetinae, Cricetulus, Enzyme-Linked Immunosorbent Assay, Female, HIV Antibodies, HIV Envelope Protein gp120, HIV Infections, HIV-1, Immunoglobulin G, Interleukin-10, Mannose, Mannosidases, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neutralization Tests, Receptors, Interleukin-10, T-Lymphocytes, Helper-Inducer

The Env glycoproteins gp120 and gp41 are used in humoral immunity-based vaccines against human immunodeficiency virus (HIV-1) infection. One among many obstacles to such a vaccine is the structural defenses of Env glycoproteins that limit their immunogenicity. For example, gp120 mannose residues can induce immunosuppressive responses in vitro, including IL-10 expression, via mannose C-type lectin receptors on antigen-presenting cells. Here, we have investigated whether mannose removal alters gp120 immunogenicity in mice. Administering demannosylated gp120 (D-gp120) in the T(H)2-skewing adjuvant Alum induced approximately 50-fold higher titers of anti-gp120 IgG, compared to unmodified gp120. While the IgG subclass profile was predominantly T(H)2-associated IgG1, Abs of the T(H)1-associated IgG2a and IgG3 subclasses were also detectable in D-gp120 recipients. Immunizing with D-gp120 also improved T-cell responses. Giving an IL-10 receptor blocking MAb together with unmodified gp120 in Alum increased the anti-gp120 IgG titer, implicating IL-10 as a possible mediator of auto-suppressive responses to gp120.

Alternate JournalVirology
PubMed ID19410272
PubMed Central IDPMC2743082
Grant ListN01 AI30030 / AI / NIAID NIH HHS / United States
R01 AI045463-11 / AI / NIAID NIH HHS / United States
R01 AI36082 / AI / NIAID NIH HHS / United States
R01 AI45463 / AI / NIAID NIH HHS / United States
R37 AI036082-16A2 / AI / NIAID NIH HHS / United States

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