Research ArticleOpen AccessGoogle Scholar indexed
α<sub>2</sub>-macroglobulin co-administered <i>in vivo</i> promotes antigen delivery and presentation
Department of Pathology, Duke University Medical Center, Durham, USA
Department of Pathology, Duke University Medical Center, Durham, USA
Department of Pathology, Duke University Medical Center, Durham, USA
Department of Pathology, Duke University Medical Center, Durham, USA
- 1 Department of Pathology, Duke University Medical Center, Durham, USA
- 2 Department of Pathology, Duke University Medical Center, Durham, USA
- 3 Department of Pathology, Duke University Medical Center, Durham, USA
- 4 Department of Pathology, Duke University Medical Center, Durham, USA
Open Journal of Immunology·Volume 02 (2012)·Pages 72–77·Published 22 June 2012·DOI10.4236/oji.2012.22009
Copy link · social · email
Abstract
Administered in vivo, covalent receptor-recognized α 2 -macroglobulin (α 2 M * )-antigen complexes enhance humoral and cell-mediated immunity. We hypothesized that in vivo α 2 M * -encapsulation could be promoted in the setting of vaccines that co-deliver α 2 M * with unbound antigen, thereby eliminating the need to prepare complexes in vitro. Mice immunized intradermally with co-delivered α 2 M * and OVA demonstrated antigen-specific immune responses, including anti-tumor responses, similar to those elicited by conjugated α 2 M * -OVA complexes. Enhanced immunity appears to result from in vivo α 2 M * -encapsulation of antigen. This finding represents a significant advancement in the development of α 2 M * as an antigen delivery vehicle capable of enhancing the presentation of subunit vaccines.
Keywordsα<sub>2</sub>-Macroglobulin-Antigen ComplexesAntigen Presentation/ProcessingVaccinationCytokinesSpleen
- Chu, C.T., Oury, T.D., Enghild, J.J. and Pizzo, S.V. (1994) Adjuvant-free in vivo targeting. Antigen delivery by alpha 2-macroglobulin enhances antibody formation. Journal of Immunology, 152, 1538-1545.
- Chu, C.T. and Pizzo, S.V. (1993) Receptor-mediated antigen delivery into macrophages. Complexing antigen to alpha2-macroglobulin enhances presentation to T cells. Journal of Immunology, 150, 48-58.
- Cianciolo, G.J., Enghild, J.J. and Pizzo, S.V. (2001) Co-valent complexes of antigen and alpha2-macroglobulin: Evidence for dramatically-increased immunogenicity. Vaccine, 20, 554-562. doi:10.1016/S0264-410X(01)00361-9
- Liao, H.X., Cianciolo, G.J., Staats, H.F., Scearce, R.M., Lapple, D.M., Stauffer, S.H., Thomasch, J.R., Pizzo, S.V., Montefiori, D.C., Hagen, M., Eldridge, J. and Haynes, B.F. (2002) Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Vaccine, 20, 2396-2403. doi:10.1016/S0264-410X(02)00090-7
- Binder, R.J., Karimeddini, D. and Srivastava, P.K. (2001) Adjuvanticity of alpha2-macroglobulin, an independent ligand for the heat shock protein receptor CD91. Journal of Immunology, 166, 4968-4972.
- Binder, R.J., Kumar, S.K. and Srivastava, P.K. (2002) Naturally formed or artificially reconstituted non-covalent alpha2-macroglobulin-peptide complexes elicit CD91-dependent cellular immunity. Cancer Immunity, 2, 16.
- Bowers, E.V., Horvath, J.J., Bond, J.E., Cianciolo, G.J. and Pizzo, S.V. (2009) Antigen delivery by alpha(2)- macroglobulin enhances the cytotoxic T lymphocyte response. Journal of Leukocyte Biology, 86, 1259-1268. doi:10.1189/jlb.1008653
- Gron, H. and Pizzo, S.V. (1998) Nonproteolytic incorporation of protein ligands into human alpha2-macroglobulin: Implications for the binding mechanism of alpha 2-macroglobulin. Biochemistry, 37, 6009-6014.
- Adlakha, C.L., Hart, J.P. and Pizzo, S.V. (2001) Kinetics of nonproteolytic incorporation of a protein ligand into thermally activated alpha2-macroglobulin: Evidence for a novel nascent state. The Journal of Biological Chemistry, 276, 41547-41552. doi:10.1074/jbc.M106357200
- Bhattacharjee, G., Gron, H. and Pizzo, S.V. (1999) Incorporation of non-proteolytic proteins by murine alpha2- macroglobulin. Biochimica et Biophysica Acta (BBA) —Protein Structure and Molecular Enzymology, 1432, 49-56. doi:10.1016/S0167-4838(99)00072-2
- Gron, H., Thogersen, I.B., Enghild, J.J. and Pizzo, S.V. (1996) Structural and functional analysis of the spontaneous reformation of the thiol ester bond in human alpha 2-macroglobulin, rat alpha1-inhibitor-3 and chemically modified derivatives. Biochemical Journal, 318, 539-545.