An HIV-1 envelope glycoprotein trimer with an embedded IL-21 domain activates human B cells. Academic Article uri icon

Overview

MeSH

  • Antigens, Viral
  • Cell Differentiation
  • Cells, Cultured
  • HIV Antibodies
  • Humans
  • Protein Engineering
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins

MeSH Major

  • B-Lymphocytes
  • HIV-1
  • Interleukins
  • Lymphocyte Activation
  • Protein Multimerization
  • env Gene Products, Human Immunodeficiency Virus

abstract

  • Broadly neutralizing antibodies (bNAbs) that target the HIV-1 envelope glycoproteins (Env) can prevent virus acquisition, but several Env properties limit its ability to induce an antibody response that is of sufficient quantity and quality. The immunogenicity of Env can be increased by fusion to co-stimulatory molecules and here we describe novel soluble Env trimers with embedded interleukin-4 (IL-4) or interleukin-21 (IL-21) domains, designed to activate B cells that recognize Env. In particular, the chimeric Env(IL-21) molecule activated B cells efficiently and induced the differentiation of antibody secreting plasmablast-like cells. We studied whether we could increase the activity of the embedded IL-21 by designing a chimeric IL-21/IL-4 (ChimIL-21/4) molecule and by introducing amino acid substitutions in the receptor binding domain of IL-21 that were predicted to enhance its binding. In addition, we incorporated IL-21 into a cleavable Env trimer and found that insertion of IL-21 did not impair Env cleavage, while Env cleavage did not impair IL-21 activity. These studies should guide the further design of chimeric proteins and Env(IL-21) may prove useful in improving antibody responses against HIV-1.

publication date

  • 2013

has subject area

  • Antigens, Viral
  • B-Lymphocytes
  • Cell Differentiation
  • Cells, Cultured
  • HIV Antibodies
  • HIV-1
  • Humans
  • Interleukins
  • Lymphocyte Activation
  • Protein Engineering
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins
  • env Gene Products, Human Immunodeficiency Virus

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3691133

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0067309

PubMed ID

  • 23826263

Additional Document Info

start page

  • e67309

volume

  • 8

number

  • 6