Enhanced immunogenicity of HIV-1 envelope gp140 proteins fused to APRIL

Gözde Isik; Kwinten Sliepen; Thijs van Montfort; Rogier W Sanders

doi:10.1371/journal.pone.0107683

Enhanced immunogenicity of HIV-1 envelope gp140 proteins fused to APRIL

PLoS One. 2014 Sep 23;9(9):e107683. doi: 10.1371/journal.pone.0107683. eCollection 2014.

Authors

Gözde Isik¹, Kwinten Sliepen¹, Thijs van Montfort¹, Rogier W Sanders²

Affiliations

¹ Laboratory of Experimental Virology, Department of Medical Microbiology Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
² Laboratory of Experimental Virology, Department of Medical Microbiology Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America.

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 types

Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / immunology
Animals
B-Cell Maturation Antigen / metabolism
HEK293 Cells
HIV Antibodies / immunology*
HIV Infections / immunology*
HIV Infections / prevention & control
HIV-1 / genetics
HIV-1 / immunology*
Humans
Mice
Rabbits
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Transmembrane Activator and CAML Interactor Protein / metabolism
Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology*
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
B-Cell Maturation Antigen
HIV Antibodies
Recombinant Fusion Proteins
Transmembrane Activator and CAML Interactor Protein
Tumor Necrosis Factor Ligand Superfamily Member 13
env Gene Products, Human Immunodeficiency Virus
gp140 envelope protein, Human immunodeficiency virus 1

Grants and funding

This work was supported by the Aids Fonds (the Netherlands), grant #2009012. RWS is a recipient of a Vidi fellowship from the Netherlands Organization for Scientific Research, and a Starting Investigator grant from the European Research Council (ERC-StG-2011-280829-SHEV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.