Share This Article:

α2-macroglobulin co-administered in vivo promotes antigen delivery and presentation

Abstract Full-Text HTML XML Download Download as PDF (Size:686KB) PP. 72-77
DOI: 10.4236/oji.2012.22009    3,011 Downloads   6,025 Views   Citations


Administered in vivo, covalent receptor-recognized α2-macroglobulin (α2M*)-antigen complexes enhance humoral and cell-mediated immunity. We hypothesized that in vivo α2M*-encapsulation could be promoted in the setting of vaccines that co-deliver α2M* with unbound antigen, thereby eliminating the need to prepare complexes in vitro. Mice immunized intradermally with co-delivered α2M* and OVA demonstrated antigen-specific immune responses, including anti-tumor responses, similar to those elicited by conjugated α2M*-OVA complexes. Enhanced immunity appears to result from in vivo α2M*-encapsulation of antigen. This finding represents a significant advancement in the development of α2M* as an antigen delivery vehicle capable of enhancing the presentation of subunit vaccines.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Bowers, E. , Bond, J. , Cianciolo, G. and Pizzo, S. (2012) α2-macroglobulin co-administered in vivo promotes antigen delivery and presentation. Open Journal of Immunology, 2, 72-77. doi: 10.4236/oji.2012.22009.


[1] 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.
[2] 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.
[3] 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
[4] 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
[5] 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.
[6] 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.
[7] 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
[8] 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.
[9] 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
[10] 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
[11] 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.
[12] Chu, C.T. and Pizzo, S.V. (1994) alpha2-Macroglobulin, complement, and biologic defense: Antigens, growth factors, microbial proteases, and receptor ligation. Laboratory Investigation, 71, 792-812.
[13] O’Hagan, D.T. and De Gregorio, E. (2009) The path to a successful vaccine adjuvant—“The long and winding road”. Drug Discovery Today, 14, 541-551.
[14] Morrot, A., Strickland, D.K., Higuichi Mde, L., Reis, M., Pedrosa, R. and Scharfstein, J. (1997) Human T cell responses against the major cysteine proteinase (cruzipain) of Trypanosoma cruzi: Role of the multifunctional alpha 2-macroglobulin receptor in antigen presentation by monocytes. International Immunology, 9, 825-834. doi:10.1093/intimm/9.6.825
[15] Huson, L.E., Authie, E., Boulange, A.F., Goldring, J.P. and Coetzer, T.H. (2009) Modulation of the immunogenicity of the Trypanosoma congolense cysteine protease, congopain, through complexation with alpha(2)-macroglobulin. Veterinary Research, 40, 52. doi:10.1051/vetres/2009036

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.