Co-immunization with an optimized plasmid-encoded immune stimulatory interleukin, high-mobility group box 1 protein, results in enhanced interferon-gamma secretion by antigen-specific CD8 T cells

与优化的质粒编码的免疫刺激白细胞介素、高迁移率族蛋白 B1 共同免疫,可增强抗原特异性 CD8 T 细胞的干扰素-γ 分泌

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作者:Gowtham Muthumani, Dominick J Laddy, Senthil G Sundaram, Paolo Fagone, Devon J Shedlock, Senthil Kannan, Ling Wu, Christopher W Chung, Karthikbabu Mallil Lankaraman, John Burns, Karuppiah Muthumani, David B Weiner

Abstract

DNA vaccination is a novel immunization strategy that has great potential for the development of vaccines and immune therapeutics. This strategy has been highly effective in mice, but is less immunogenic in non-human primates and in humans. Enhancing DNA vaccine potency remains a challenge. It is likely that antigen-presenting cells (APCs), and especially dendritic cells (DCs), play a significant role in the presentation of the vaccine antigen to the immune system. A new study reports the synergistic recruitment, expansion and activation of DCs in vivo by high-mobility group box 1 (HMGB1) protein. Such combinational strategies for delivering vaccine in a single, simple platform will hypothetically bolster the cellular immunity in vivo. Here, we combined plasmid encoding human immunodeficiency virus-1 (HIV-1) Gag and Env with an HMGB1 plasmid as a DNA adjuvant in BALB/c mice (by intramuscular immunization via electroporation), and humoral and cellular responses were measured. Co-administration of this potent immunostimulatory adjuvant strongly enhanced the cellular interferon-gamma (IFN-gamma) and humoral immune response compared with that obtained in mice immunized with vaccine only. Our results show that co-immunization with HMGB1 can have a strong adjuvant activity, driving strong cellular and humoral immunity that may be an effective immunological adjuvant in DNA vaccination against HIV-1.

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