Improved vaccines by targeting to dendritic cells

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  Project Leader
  Professor William (Bill) Heath

  wrheath@unimelb.edu. au

  View researcher's webpage

  +61 3 8344 5682

Project Details

Targeting Clec9A

Potent immune responses can be induced by targeting antigens to surface receptors on dendritic cells (DCs). Our previous studies have shown that targeting antigens to Clec9A, a receptor specifically expressed by CD8+ DC, induces potent humoral immunity and, in contrast to other receptors, does not require adjuvant. Dissecting the basis for strong humoral priming through Clec9A targeting will improve our general understanding of how an efficient humoral immune response is generated and will also provide potential novel strategies for designing new vaccines. The project aims to understand how such targeting strategy foster interaction between CD8+ DCs, CD4+ T cells and B cells. In particular, we are exploring previously unappreciated ability of CD8+ DCs to retain and present native antigen to drive B cell response using various experimental approaches including intra-vital 2-photon imaging of spleen and lymph node.

Understanding the Immunostimulatory capacity of CpG

DEC-205 is a C-type lectin-like receptor expressed at high levels on the surface of CD8+ dendritic cells, and at lower levels on other immune cells. We have previously shown that DEC-205 is a receptor for CpG oligonucleotides (ODNs) that is required for their optimal immunostimulatory activity. As CpG ODNs are synthetic compounds often used as adjuvants to enhance immune responses, a greater understanding of this interaction would lead to advances in ODN adjuvant safety and efficacy.

1. We aim to determine the molecular characteristics of ODNs required for efficient DEC-205 binding. Understanding the molecular requirements for DEC-205 binding will not only inform the design of synthetic ODNs, but may also provide clues about the nature of the biological ligand of DEC-205, which is currently unknown.
2. We are examining the role of DEC-205 in various aspects of CpG ODN function. Understanding the immunological outcomes of DEC-205 binding will provide the potential for greater control of these effects of ODNs. For instance, we are investigating whether DEC-205 binding can be manipulated to alter the immunostimulatory capabilities of CpG ODNs.

Researchers

Yu (Alex) Kato
Jessica Li, Monash University
Irene Caminschi, Monash University