Alum Increases Antigen Uptake, Reduces Antigen Degradation and Sustains Antigen Presentation by DCs in Vitro

Overview

Journal Immunol Lett

Specialty Allergy & Immunology

Date 2012 Jun 27

PMID 22732235

Citations 61

Authors

Tirth R Ghimire

Robert A Benson

Paul Garside

James M Brewer

Affiliations

Soon will be listed here.

Abstract

Aluminium adjuvants (alum) have been the only widely approved adjuvants for use in human vaccines since the 1920s, however, the mechanism of action of these adjuvants remains elusive. Due to increasing demand for novel adjuvants, a clearer understanding of the mechanisms that allow these important agents to affect adaptive immune responses will make a significant contribution to the rational design of future vaccines. Using a novel approach to tracking antigen and antigen presentation, we demonstrate that alum induces higher antigen accumulation and increased antigen presentation by dendritic cells (DCs) in vitro. Antigen accumulation was 100-fold higher and antigen presentation 10-fold higher following alum treatment when compared with soluble protein alone. We also observed that alum causes an initial reduction in presentation compared with soluble antigen, but eventually increases the magnitude and duration of antigen presentation. This was associated with reduced protein degradation in DCs following alum treatment. These studies demonstrate the dynamic alterations in antigen processing and presentation induced by alum that underlie enhanced DC function in response to this adjuvant.

Citing Articles

Basic Properties and Development Status of Aluminum Adjuvants Used for Vaccines.

Lan J, Feng D, He X, Zhang Q, Zhang R Vaccines (Basel). 2024; 12(10).

PMID: 39460352 PMC: 11511158. DOI: 10.3390/vaccines12101187.

Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling.

Cao A, Wang Y, Shen Y, Liu Y, Liu J, Wang Y Nutrients. 2024; 16(16).

PMID: 39203802 PMC: 11356829. DOI: 10.3390/nu16162665.

Specific targeting of cancer vaccines to antigen-presenting cells via an endogenous TLR2/6 ligand derived from cysteinyl-tRNA synthetase 1.

Kim H, Cho S, Kim S, Song E, Jung W, Shin Y Mol Ther. 2024; 32(10):3597-3617.

PMID: 39066478 PMC: 11489552. DOI: 10.1016/j.ymthe.2024.07.014.

Production of Antibodies to Peptide Targets Using Hybridoma Technology.

Trier N, Friis T Methods Mol Biol. 2024; 2821:135-156.

PMID: 38997486 DOI: 10.1007/978-1-0716-3914-6_11.

A Comparative Study of the Effects of Al(OH) and AlPO Adjuvants on the Production of Neutralizing Antibodies (NAbs) against Bovine parainfluenza Virus Type 3 (BPIV3) in Guinea Pigs.

Heidary R, Nikbakht Brujeni G, Lotfi M, Hajizadeh A, Yousefi A Arch Razi Inst. 2024; 78(6):1779-1786.

PMID: 38828184 PMC: 11139405. DOI: 10.32592/ARI.2023.78.6.1779.

References

Rudensky AYu , Rath S, Preston-Hurlburt P, Murphy D, Janeway Jr C . On the complexity of self. Nature. 1991; 353(6345):660-2. DOI: 10.1038/353660a0. View

Ulanova M, Tarkowski A, Hahn-Zoric M, Hanson L . The Common vaccine adjuvant aluminum hydroxide up-regulates accessory properties of human monocytes via an interleukin-4-dependent mechanism. Infect Immun. 2001; 69(2):1151-9. PMC: 97997. DOI: 10.1128/IAI.69.2.1151-1159.2001. View

Lutz M, Kukutsch N, OGILVIE A, Rossner S, Koch F, Romani N . An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 1999; 223(1):77-92. DOI: 10.1016/s0022-1759(98)00204-x. View

Zinkernagel R . Localization dose and time of antigens determine immune reactivity. Semin Immunol. 2000; 12(3):163-71; discussion 257-344. DOI: 10.1006/smim.2000.0253. View

Celli S, Lemaitre F, Bousso P . Real-time manipulation of T cell-dendritic cell interactions in vivo reveals the importance of prolonged contacts for CD4+ T cell activation. Immunity. 2007; 27(4):625-34. DOI: 10.1016/j.immuni.2007.08.018. View

Villadangos J, Ploegh H . Proteolysis in MHC class II antigen presentation: who's in charge?. Immunity. 2001; 12(3):233-9. DOI: 10.1016/s1074-7613(00)80176-4. View

Iezzi G, Karjalainen K, Lanzavecchia A . The duration of antigenic stimulation determines the fate of naive and effector T cells. Immunity. 1998; 8(1):89-95. DOI: 10.1016/s1074-7613(00)80461-6. View

Rudensky A, Preston-Hurlburt P, Hong S, Barlow A, Janeway Jr C . Sequence analysis of peptides bound to MHC class II molecules. Nature. 1991; 353(6345):622-7. DOI: 10.1038/353622a0. View

Morefield G, Sokolovska A, Jiang D, HogenEsch H, Robinson J, Hem S . Role of aluminum-containing adjuvants in antigen internalization by dendritic cells in vitro. Vaccine. 2005; 23(13):1588-95. DOI: 10.1016/j.vaccine.2004.07.050. View

10.

Itano A, McSorley S, Reinhardt R, Ehst B, Ingulli E, Rudensky A . Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity. 2003; 19(1):47-57. DOI: 10.1016/s1074-7613(03)00175-4. View

11.

Nakagawa T, Rudensky A . The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation. Immunol Rev. 2000; 172:121-9. DOI: 10.1111/j.1600-065x.1999.tb01361.x. View

12.

Bajenoff M, Granjeaud S, Guerder S . The strategy of T cell antigen-presenting cell encounter in antigen-draining lymph nodes revealed by imaging of initial T cell activation. J Exp Med. 2003; 198(5):715-24. PMC: 2194192. DOI: 10.1084/jem.20030167. View

13.

Shin J, Ebersold M, Pypaert M, Delamarre L, Hartley A, Mellman I . Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination. Nature. 2006; 444(7115):115-8. DOI: 10.1038/nature05261. View

14.

Nelson C, Vidavsky I, Viner N, Gross M, UNANUE E . Amino-terminal trimming of peptides for presentation on major histocompatibility complex class II molecules. Proc Natl Acad Sci U S A. 1997; 94(2):628-33. PMC: 19564. DOI: 10.1073/pnas.94.2.628. View

15.

Schrum A, Turka L . The proliferative capacity of individual naive CD4(+) T cells is amplified by prolonged T cell antigen receptor triggering. J Exp Med. 2002; 196(6):793-803. PMC: 2194051. DOI: 10.1084/jem.20020158. View

16.

Rimaniol A, Gras G, Clayette P . In vitro interactions between macrophages and aluminum-containing adjuvants. Vaccine. 2007; 25(37-38):6784-92. DOI: 10.1016/j.vaccine.2007.06.051. View

17.

Brewer J . (How) do aluminium adjuvants work?. Immunol Lett. 2005; 102(1):10-5. DOI: 10.1016/j.imlet.2005.08.002. View

18.

Sokolovska A, Hem S, HogenEsch H . Activation of dendritic cells and induction of CD4(+) T cell differentiation by aluminum-containing adjuvants. Vaccine. 2007; 25(23):4575-85. DOI: 10.1016/j.vaccine.2007.03.045. View

19.

Delamarre L, Couture R, Mellman I, Trombetta E . Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis. J Exp Med. 2006; 203(9):2049-55. PMC: 2118388. DOI: 10.1084/jem.20052442. View

20.

Trombetta E, Ebersold M, Garrett W, Pypaert M, Mellman I . Activation of lysosomal function during dendritic cell maturation. Science. 2003; 299(5611):1400-3. DOI: 10.1126/science.1080106. View