Targeted Programming of the Lymph Node Environment Causes Evolution of Local and Systemic Immunity

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• 作者：James I. Andorko ; Joshua M. Gammon…
• 刊名：Cellular and Molecular Bioengineering
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：9
• 期：3
• 页码：418-432
• 全文大小：2,893 KB
• 刊物类别：Engineering
• 刊物主题：Biomedical Engineering
  Mechanics
  Continuum Mechanics and Mechanics of Materials
  Biophysics and Biomedical Physics
  Cell Biology
  
• 出版者：Springer New York
• ISSN：1865-5033
• 卷排序：9

文摘

Biomaterial vaccines offer cargo protection, targeting, and co-delivery of signals to immune organs such as lymph nodes (LNs), tissues that coordinate adaptive immunity. Understanding how individual vaccine components impact immune response has been difficult owing to the systemic nature of delivery. Direct intra-lymph node (i.LN.) injection offers a unique opportunity to dissect how the doses, kinetics, and combinations of signals reaching LNs influence the LN environment. Here, i.LN. injection was used as a tool to study the local and systemic responses to vaccines comprised of soluble antigen and degradable polymer particles encapsulating toll-like receptor agonists as adjuvants. Microparticle vaccines increased antigen presenting cells and lymphocytes in LNs, enhancing activation of these cells. Enumeration of antigen-specific CD8+ T cells in blood revealed expansion over 7 days, followed by a contraction period over 1 month as memory developed. Extending this strategy to conserved mouse and human tumor antigens resulted in tumor antigen-specific primary and recall responses by CD8+ T cells. During challenge with an aggressive metastatic melanoma model, i.LN. delivery of depots slowed tumor growth more than a potent human vaccine adjuvant, demonstrating local treatment of a target immunological site can promote responses that are potent, systemic, and antigen-specific.KeywordsLymph nodeVaccineAdjuvantMicroparticle and nanoparticleCancerImmunotherapy