Open AccessCD40L-Containing Virus-Like Particle as a Candidate HIV-1 Vaccine Targeting Dendritic Cells
Author(s) -
David Franco,
Weimin Liu,
David F. Gardiner,
Beatrice H. Hahn,
David D. Ho
Publication year - 2011
Publication title -
journal of acquired immune deficiency syndromes
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.162
H-Index - 157
eISSN - 1944-7884
pISSN - 1525-4135
DOI - 10.1097/qai.0b013e31820b844e
Subject(s) - cd40 , immunogenicity , immune system , dendritic cell , antigen , immunology , virology , hiv antigens , virus like particle , biology , in vitro , microbiology and biotechnology , virus , cytotoxic t cell , recombinant dna , viral disease , biochemistry , gene
The central role of dendritic cell (DC) in mounting an immune response to a novel antigen is now well established. We sought to demonstrate the use of a particular vaccine strategy based on directing HIV-1 Gag proteins to DCs in conjunction with an activation signal. CD40L was expressed on the surface of virus-like particles (VLPs) to target HIV-1 Gag antigens to the CD40 receptor on DCs, whereas CD40L-CD40 interaction would also result in cellular activation. Multiple CD40L VLP constructs were made and evaluated in vitro and in vivo. Indeed, one VLP that expressed CD40L to the highest level showed greatest capacity to activate DCs in vitro. Correspondingly, this CD40L-VLP also proved to be most immunogenic in mice in raising both humoral and cellular responses to HIV-1 Gag. Confirmatory studies were performed to demonstrate the increased immunogenicity of CD40L-VLP is no longer observed when tested in CD40-/- mice. Our findings lend support to the belief that vaccine strategies that both target and activate DCs could yield a superior immune response.