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

• Published in: PloS one Vol. 9; no. 9; p. e107683
• Main Authors: Isik, Gözde, Sliepen, Kwinten, van Montfort, Thijs, Sanders, Rogier W
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.09.2014; Public Library of Science (PLoS)
• Subjects: AIDS vaccines; AIDS Vaccines - immunology; Animals; Antibodies; Antigens; APRIL protein; Autoantibodies; Autoimmunity; B cells; B-Cell Maturation Antigen - metabolism; Biology and Life Sciences; CD40L protein; Cell activation; Comparative analysis; Costimulator; Cytokines; Dendritic cells; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Glycoproteins; Granulocyte-macrophage colony-stimulating factor; Guillain-Barre syndrome; HEK293 Cells; HIV; HIV Antibodies - immunology; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Humans; Humoral immunity; Immune system; Immunity; Immunogenicity; Immunoglobulins; Infections; Interleukin 21; Laboratories; Ligands; Lymphocytes B; Mice; Proteins; Rabbits; Receptors; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Transmembrane Activator and CAML Interactor Protein - metabolism; Tumor necrosis factor; Tumor Necrosis Factor Ligand Superfamily Member 13 - genetics; Tumor Necrosis Factor Ligand Superfamily Member 13 - immunology; Vaccines; Virology; New York; United States > US; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0107683

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.