Enhanced immunogenicity of HIV-1 envelope gp140 proteins fused to APRIL. Academic Article uri icon

Overview

abstract

  • Current HIV-1 vaccines based on the HIV-1 envelope glycoprotein spike (Env), the only relevant target for broadly neutralizing antibodies, are unable to induce protective immunity. Env immunogenicity can be enhanced by fusion to costimulatory molecules involved in B cell activation, such as APRIL and CD40L. Here, we found that Env-APRIL signaled through the two receptors, BCMA and TACI. In rabbits, Env-APRIL induced significantly higher antibody responses against Env compared to unconjugated Env, while the antibody responses against the APRIL component were negligible. To extend this finding, we tested Env-APRIL in mice and found minimal antibody responses against APRIL. Furthermore, Env-CD40L did not induce significant anti-CD40L responses. Thus, in contrast to the 4-helix cytokines IL-21 and GM-CSF, the TNF-superfamily members CD40L and APRIL induced negligible autoantibodies. This study confirms and extends previous work and shows that fusion of Env-based immunogens to APRIL can improve Env immunogenicity and might help in designing HIV vaccines that induce protective humoral immunity.

publication date

  • September 23, 2014

Research

keywords

  • HIV Antibodies
  • HIV Infections
  • HIV-1
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • env Gene Products, Human Immunodeficiency Virus

Identity

PubMed Central ID

  • PMC4172553

Scopus Document Identifier

  • 84907573575

Digital Object Identifier (DOI)

  • 10.1073/pnas.1217537110

PubMed ID

  • 25247707

Additional Document Info

volume

  • 9

issue

  • 9