Enzymatic removal of mannose moieties can increase the immune response to HIV-1 gp120 in vivo Academic Article uri icon

Overview

MeSH Major

  • AIDS Vaccines
  • HIV Envelope Protein gp120
  • HIV Infections
  • Mannose
  • T-Lymphocytes, Helper-Inducer

abstract

  • 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.

publication date

  • May 26, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2743082

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2009.04.001

PubMed ID

  • 19410272

Additional Document Info

start page

  • 108

end page

  • 21

volume

  • 389

number

  • 1-2