免疫
佐剂
抗原
CD8型
牛痘
细胞毒性T细胞
病毒学
生物
免疫学
医学
化学
生物化学
重组DNA
基因
体外
作者
Frances C. Knight,Pavlo Gilchuk,Amrendra Kumar,Kyle W. Becker,Sema Sevimli,Max E. Jacobson,Naveen Chandra Suryadevara,Lihong Wang-Bishop,Kelli L. Boyd,James E. Crowe,Sebastian Joyce,John T. Wilson
出处
期刊:ACS Nano
[American Chemical Society]
日期:2019-09-25
卷期号:13 (10): 10939-10960
被引量:82
标识
DOI:10.1021/acsnano.9b00326
摘要
Tissue-resident memory T cells (TRM) patrol nonlymphoid organs and provide superior protection against pathogens that commonly infect mucosal and barrier tissues, such as the lungs, intestine, liver, and skin. Thus, there is a need for vaccine technologies that can induce a robust, protective TRM response in these tissues. Nanoparticle (NP) vaccines offer important advantages over conventional vaccines; however, there has been minimal investigation into the design of NP-based vaccines for eliciting TRM responses. Here, we describe a pH-responsive polymeric nanoparticle vaccine for generating antigen-specific CD8+ TRM cells in the lungs. With a single intranasal dose, the NP vaccine elicited airway- and lung-resident CD8+ TRM cells and protected against respiratory virus challenge in both sublethal (vaccinia) and lethal (influenza) infection models for up to 9 weeks after immunization. In elucidating the contribution of material properties to the resulting TRM response, we found that the pH-responsive activity of the carrier was important, as a structurally analogous non-pH-responsive control carrier elicited significantly fewer lung-resident CD8+ T cells. We also demonstrated that dual-delivery of protein antigen and nucleic acid adjuvant on the same NP substantially enhanced the magnitude, functionality, and longevity of the antigen-specific CD8+ TRM response in the lungs. Compared to administration of soluble antigen and adjuvant, the NP also mediated retention of vaccine cargo in pulmonary antigen-presenting cells (APCs), enhanced APC activation, and increased production of TRM-related cytokines. Overall, these data suggest a promising vaccine platform technology for rapid generation of protective CD8+ TRM cells in the lungs.
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