Open AccessAn Engineered Non-Toxic Superantigen Increases Cross Presentation of Hepatitis B Virus Nucleocapsids by Human Dendritic Cells
Author(s) -
Julie McIntosh,
Kristy Manning,
Shilpa Chokshi,
Nikolai V. Naoumov,
John D. Fraser,
P. Rod Dunbar,
John A. Taylor
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0093598
Subject(s) - hbcag , epitope , cross presentation , superantigen , t cell , microbiology and biotechnology , antigen presenting cell , biology , antigen , virology , hepatitis b virus , chemistry , virus , hbsag , immune system , immunology
Virus like particles (VLPs) are potent immunogens capable of priming strong protective antibody responses due to their repetitive structural arrangement and affinity for specific B cell receptors. By contrast, T cell responses to VLPs can be weak due to inefficient uptake and processing by antigen presenting cells. We report here a novel strategy for increasing the T cell reactivity of a VLP, the nucleocapsid of hepatitis B virus, through covalent coupling of M1, an engineered form of the Streptococcal superantigen SMEZ2, that binds MHC II with high affinity but lacks its T cell mitogenic capability. M1:HBcAg conjugates bound to dendritic cells and were efficiently endocytosed into late endosomes. Human dendritic cells pulsed with M1:HBcAgs stimulated HBV-specific CD8 + T cells more effectively than cells pulsed with native capsids indicating that the modified VLP was more effectively cross presented by APCs. Coupling of M1 was also able to induce significantly greater reactivity of human CD4 + T cells specific for a common T-helper epitope. These studies indicate the potential of recombinant superantigens to act as flexible molecular adjuvants that can be incorporated into various subunit vaccine platforms leading to enhanced T cell reactivity in humans.