B lymphocytes as antigen-presenting cell-based genetic vaccines

Authors: Zanetti, Maurizio; Castiglioni, Paola; Rizzi, Marta; Wheeler, Matthew; Gerloni, Mara

Source: Immunological Reviews, Volume 199, Number 1, June 2004 , pp. 264-278(15)

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Abstract:

Summary:

Inoculation of plasmid DNA is a simple way to immunize, but it is characterized by low immunogenicity, which has hampered the development of effective DNA vaccines for human use. Here, we discuss how poor immunogenicity can be solved and present our proposal: genetically programmed B lymphocytes as antigen-presenting cell (APC) vaccines. First, we demonstrate that mature B lymphocytes take up plasmid DNA spontaneously, i.e., in the absence of any facilitating molecule or event, spontaneous lymphocyte transgenesis. Second, we demonstrate that transgenic B lymphocytes are easily and reproducibly turned into functional APCs with dual characteristics: upregulation of costimulatory molecules and endogenous synthesis of antigen. Used as immunogens in mice, transgenic B lymphocytes induce robust and long-lasting T-cell immunity after single intravenous injection. Surprisingly, immunity and protection against lethal virus challenge can be obtained with a single intravenous injection of 3 × 10² transgenic lymphocytes. The new approach is discussed relative to the advantage of targeting secondary lymphoid organs with genetically programmed B lymphocytes and the advantage offered with respect to low antigen dose. We suggest that these properties reflect on simple characteristics, such as time synchronization and initial localization to secondary lymphoid organs of APCs endowed with protracted synthesis and presentation of antigen to T cells.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.0105-2896.2004.00152.x

Affiliations: 1: The Department of Medicine and Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Publication date: 2004-06-01