Linda Klavinskis, PhD
Senior Lecturer Immunobiology
Tel: +44 (0) 20 7188 0151
Fax: +44 (0) 20 7188 3385
Dendritic cells are central to immune regulation because of their roles in inducing protective immunity against pathogens while maintaining tolerance to self antigens. Fundamental to their immune regulatory role is their capacity to integrate qualitatively distinct signals from their environment that de facto inhibit or promote pro-inflammatory immune responses, which may result in vastly different outcomes for the host, ranging from tolerogenic or regulatory responses to protective adaptive Th1, Th2 or Th17 responses. Our laboratory is interested in both understanding and exploiting basic mechanisms by which dendritic cells control innate and adaptive immunity in the context of developing effective adjuvants for clinical use, and vaccines for infectious diseases such as HIV.
Within this broad context, our current interests include:
1. Exploring HIV-1 vaccine elicited CD8 T lymphocyte epitope immunondominance with the goal of inducing a broader protective T cell response. We are investigating how the diversity, magnitude and quality of CD8 T cell responses can be enhanced by combinatorial modification and re-arrangement of epitopes within the antigen.
2. Targeted delivery of polymer coated adenoviral vectored vaccines to dendritic cells. We are developing a ‘stealth’ vaccine vector based upon Adenovirus type 5. We are using novel polymers coupled to specific dendritic cell ligands so as to avoid pre-existing immunity to Ad5 and to specifically target the vector to dendritic cell subtypes.
3. Defining the immune potentiating and modulating activity of a novel microbial derived adjuvant identified in our laboratory. We are taking both molecular profiling techniques and cellular approaches, to understand the signaling networks modulated by the novel derived adjuvant in dendritic cells. Our goals are to exploit this adjuvant to (i) enhance CD8 T cell responses against infectious disease and tumour antigens and (ii) re-direct detrimental Th2 responses in allergic disease.
4.Investigating the immunology of the intestine, using ex vivo organ culture systems to address (i) what are the basic features of immune cells in the human healthy intestinal mucosa and (ii) how do cells of the intestinal immune system handle potential pathogens and vaccines and (Iii) how can we enhance this process to enable the design of effective mucosal vaccines.
Soderquest K, Walzer T, Zafirova B, Klavinskis LS, Vivier E, Lord GM, Martín-Fontecha A. 2011. Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses. J Immunol. 2011 Mar 15;186(6):3304-8
Harandi AM, Medaglini D, Shattock RJ et al ; Working Group convened by EUROPRISE. 2010. Vaccine adjuvants: a priority for vaccine research. Vaccine ;28(12):2363-6
Benlahrech A, Harris J, Meiser A, Papagatsias T, Hornig J, Hayes P, Lieber A, Athanasopoulos T, Bachy V, Csomor E, Daniels R, Fisher K, Gotch F, Seymour L, Logan K, Barbagallo R, Klavinskis L, Dickson G, Patterson S. (2009). Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc Natl. Acad Sci U S A. 24;106(47):19940-5.
Cerovic V, Barnes ACG, Jenkins C, Milling S, MacPherson G and Klavinskis L. S. (Feb 2009). Hyporesponsiveness of intestinal dendritic cells to TLR stimulation is limited to TLR4. J. Immunol. 15: 182(4): 2405 – 15.
Article highlighted in Nature (Research News) June 18th 2009 “An infection biologist points out an outstanding issue in mucosal immunology."
Benlahrech A; Donaghy H; Rozis G; Goodier M; Klavinskis L; Gotch F; Patterson S. (Jan 2009). Human NK Cell Up-regulation of CD69, HLA-DR, Interferon gamma Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways. SENSORS-BASEL. 9:386-403
Smyth LA, Harker N, Turnbull W, El-Doueik H, Klavinskis L, Kioussis D, Lombardi G, Lechler R.(2008). The relative efficiency of acquisition of MHC: peptide complexes and cross-presentation depends on dendritic cell type. J Immunol. 2008 Sep 1;181(5):3212-20.
Barnes AG, Cerovic V, Hobson P and Klavinskis L.S. 2007. Bacillus subtilis spores: a novel microparticle adjuvant which can instruct a balanced Th1 and Th2 immune response to specific antigen. Eur. J. Immunol. 37(6): 1538-1547.
Peters BS, Janko W, Vardas E, Panayotakopoulos G, Fast P, Schmidt C, Gilmour J, Bogoshi M, Dally L, Klavinskis L, Farah B, Tarragona T, Bart PA, McMichael AJ, Pantaleo G, Hanke T and Bwayo J. 2007. Studies of a prophylactic HIV-1 vaccine candidate based on modified vaccinia virus Ankara (MVA) with and without DNA priming: effects of dosage and route on safety and immunogenicity. Vaccine. 25(11):2120-7.
Yrlid U, Cerovic V, Milling S, Jenkins C, Klavinskis L. S. and MacPherson G. 2006. Plasmacytoid dendritic cells do not migrate in intestinal or hepatic lymph. J. Immunol. 177(9): 6115-21.
Yrlid U, Cerovic V, Milling S, Jenkins C, Klavinskis L. S. and MacPherson G. 2006. A distinct subset of dendritic cells responds selectively to oral TLR7/8 stimulation. Eur. J. Immunol. 36 (10): 2639-48.
Klavinskis L. S. Chapter 45. Nucleic Acid Vaccines. 2006. Topley and Wilsons Microbiology and Microbial Infections - Immunology 10th Edition, Ed. Stefan H E Kaufmann, Michael W Steward , Edward Arnold
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