title: Exploring the vaccine potential of Dec-205 targeting in Mycobacterium tuberculosis infection in mice.
abstract: Protein subunit vaccines are an attractive mode of immunisation against infectious diseases but the approach is hampered by the lack of suitable adjuvants for human use. We investigated if antigen targeting to the endocytic cell receptor Dec-205 on dendritic cells (DCs) could induce a protective immune response to Mycobacterium tuberculosis (MTB) infection in the absence of conventional adjuvants. Dec-205 receptor expressed by several subsets of DC has been shown in previous studies to be an efficient endocytic receptor for inducing both humoral and cellular immune responses, but this immunisation approach has not been tested in an experimental model of infection. We therefore prepared chemical conjugates of an anti-mouse Dec-205 monoclonal antibody (mAb) and the highly immunogenic antigen 85B (Ag85B) of MTB and showed that they bound efficiently to bone-marrow derived DC. Moreover, DC stimulated in vitro with Dec-205 conjugates could induce proliferation of splenocytes from Ag85B-immunised mice, while the negative control conjugates failed to do so. Following immunisation of mice with the anti-Dec-205-Ag85B conjugates administered together with a co-stimulatory anti-CD40 mAb, antigen-specific humoral and cellular responses were detected. Although the conjugates induced a strong Ag85B-specific humoral response, T cell proliferation and interferon-γ production were observed only when the conjugates were used to boost BCG vaccine. Importantly though, the conjugate vaccine did not offer significant protection against MTB challenge when used on its own or as a boost to BCG. Therefore, we conclude that Ag85B-based vaccine targeting to Dec-205 alone is not a sufficiently robust vaccination strategy for tuberculosis, although this approach might be more successful with other antigens or infections.
authors.affiliation: Division of Clinical Sciences, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom.
authors.forename: Elena
authors.initials: E
authors.lastname: Stylianou
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pepponi
authors.forename: Craig J
authors.initials: CJ
authors.lastname: van Dolleweerd
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Paul
authors.forename: Julian K
authors.initials: JK
authors.lastname: Ma
authors.forename: Rajko
authors.initials: R
authors.lastname: Reljic
mesh_terms: D000217:Acyltransferases / Q000276:immunology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006825:Hybridomas; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D018796:Immunoconjugates / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051381:Rats; D011956:Receptors, Cell Surface / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015703:Antigens, CD; D001426:Bacterial Proteins; C093569:DEC-205 receptor; D018796:Immunoconjugates; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis