title: Enhanced immunogenicity of HIV-1 envelope gp140 proteins fused to APRIL.
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.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Gözde
authors.initials: G
authors.lastname: Isik
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Kwinten
authors.initials: K
authors.lastname: Sliepen
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: van Montfort
authors.affiliation: 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.
authors.forename: Rogier W
authors.initials: RW
authors.lastname: Sanders
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D053301:B-Cell Maturation Antigen / Q000378:metabolism; D057809:HEK293 Cells; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051379:Mice; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D053301:B-Cell Maturation Antigen; D015483:HIV Antibodies; D011993:Recombinant Fusion Proteins; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1