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Vaccine2012; 30(30); 4532-4542; doi: 10.1016/j.vaccine.2012.04.030

Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

Abstract: Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity.
Published by Elsevier Ltd.
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Publication Date: 2012-04-21 PubMed ID: 22531556PubMed Central: PMC3519277DOI: 10.1016/j.vaccine.2012.04.030Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research focuses on understanding the role of dendritic cells (DCs) in adjuvant activity stimulated by Venezuelan equine encephalitis virus replicon particles (VRP). The researchers found that VRP-infected dendritic cells could induce an inflammatory state similar to actual VRP injection and were enough to stimulate robust adjuvant activity.

Understand the Role of Dendritic Cells in VRP Adjuvant Activity

  • The study initially looks at the role of dendritic cells in bolstering the immune response to VRP. A replicon particle is an infectious but non-propagating particle derived from a virus, and in this case, the Venezuelan equine encephalitis virus.
  • Previous studies have confirmed that VEE and its replicon particles can target multiple cell types, including dendritic cells. However, how these cells contribute to the adjuvant activity of VRP, the act of enhancing the body’s immune response to an antigen, hadn’t been studied in depth before.

Findings on Inflammatory Dendritic Cells

  • Through analysis of VRP’s impact in the draining lymph node, it was discovered that VRP induces a rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells.
  • The VRP was seen as infecting these inflammatory DCs, classical DCs, and macrophages, but it was less efficient in infecting other cell types. This suggested a preference of VRP for these cell categories.
  • When dendritic cells were depleted, it suggested that VRP interaction with classical DCs was a requirement for recruiting inflammatory DCs, inducing several cytokines, and for secure transport of VRP to the draining lymph node.

Impact of VRP-infected Dendritic Cells

  • The DCs infected with VRP in a lab setting were seen as enhancing the antigen-specific responses by CD4 and CD8 T cells. This implies that VRP-infected DCs play a significant role in bolstering immune response.
  • By transferring VRP-infected DCs into mice, the researchers demonstrated that these DCs could generate an inflammatory state resembling that achieved by VRP injection.
  • The most critical finding was that VRP-infected DCs were sufficient to establish robust adjuvant activity in the mice, comparable to the output of direct VRP injection.

Conclusion of the Research

  • Based on these findings mentioned above, the study concluded that VRP infect and activate both classical and inflammatory DCs, and these DCs become mediators of VRP adjuvant activity.
  • The role of infected DCs in mediating adjuvant activity provides potential for therapeutic applications in boosting immune responses in various medical scenarios.

Cite This Article

APA
Tonkin DR, Whitmore A, Johnston RE, Barro M. (2012). Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles. Vaccine, 30(30), 4532-4542. https://doi.org/10.1016/j.vaccine.2012.04.030

Publication

Vaccine
ISSN: 1873-2518
NlmUniqueID: 8406899
Country: Netherlands
Language: English
Volume: 30
Issue: 30
Pages: 4532-4542

Researcher Affiliations

Tonkin, Daniel R
  • Global Vaccines Inc, 7020 Kit Creek Rd, Ste. 240, PO Box 14827, Research Triangle Park, NC 27709, USA. dtonkin@globalvaccines.org
Whitmore, Alan
    Johnston, Robert E
      Barro, Mario

        MeSH Terms

        • Adjuvants, Immunologic / pharmacology
        • Animals
        • Antibodies, Viral / blood
        • Cytokines / immunology
        • Dendritic Cells / immunology
        • Dendritic Cells / virology
        • Encephalitis Virus, Venezuelan Equine / immunology
        • Female
        • Immunity, Cellular
        • Immunity, Mucosal
        • Inflammation / immunology
        • Lymph Nodes / immunology
        • Lymphocyte Activation
        • Mice
        • Mice, Inbred BALB C
        • Mice, Inbred C57BL
        • Mice, Transgenic
        • Replicon / immunology
        • T-Lymphocytes / immunology
        • Virion / immunology

        Grant Funding

        • U01 AI070976 / NIAID NIH HHS
        • F32AI082894 / NIAID NIH HHS
        • R01-AI088250 / NIAID NIH HHS
        • R01 AI088250 / NIAID NIH HHS
        • U01-AI070976 / NIAID NIH HHS
        • F32 AI082894 / NIAID NIH HHS

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        Citations

        This article has been cited 15 times.
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