Malmö University Publications
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  • 1.
    Danielsson, Ravi
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Eriksson, Håkan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Aluminium adjuvants in vaccines: A way to modulate the immune response2021In: Seminars in Cell and Developmental Biology, ISSN 1084-9521, E-ISSN 1096-3634, Vol. 115, p. 3-9, article id S1084-9521(20)30202-0Article in journal (Refereed)
    Abstract [en]

    Aluminium salts have been used as adjuvants in vaccines for almost a century, but still no clear understanding of the mechanisms behind the immune stimulating properties of aluminium based adjuvants is recognized. Aluminium adjuvants consist of aggregates and upon administration of a vaccine, the aggregates will be recognized and phagocytosed by sentinel cells such as macrophages or dendritic cells. The adjuvant aggregates will persist intracellularly, maintaining a saturated intracellular concentration of aluminium ions over an extended time. Macrophages and dendritic cells are pivotal cells of the innate immune system, linking the innate and adaptive immune systems, and become inflammatory and antigen-presenting upon activation, thus mediating the initiation of the adaptive immune system. Both types of cell are highly adaptable, and this review will discuss and highlight how the occurrence of intracellular aluminium ions over an extended time may induce the polarization of macrophages into inflammatory and antigen presenting M1 macrophages by affecting the: endosomal pH; formation of reactive oxygen species (ROS); stability of the phagosomal membrane; release of damage associated molecular patterns (DAMPs); and metabolism (metabolic re-programming). This review emphasizes that a persistent intracellular presence of aluminium ions over an extended time has the potential to affect the functionality of sentinel cells of the innate immune system, inducing polarization and activation. The immune stimulating properties of aluminium adjuvants is presumably mediated by several discrete events, however, a persistent intracellular presence of aluminium ions appears to be a key factor regarding the immune stimulating properties of aluminium based adjuvants.

  • 2.
    Danielsson, Ravi
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ferey, Nathan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Univ Clermont Auvergne, Polytech Clermont Ferrand, F-63001 Clermont ferrand, France..
    Mile, Irene
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Eriksson, Håkan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Metabolic Reprogramming of Macrophages upon In Vitro Incubation with Aluminum-Based Adjuvant2023In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 24, no 5, article id 4409Article in journal (Refereed)
    Abstract [en]

    Aluminum-based adjuvants have been extensively used in vaccines. Despite their widespread use, the mechanism behind the immune stimulation properties of these adjuvants is not fully understood. Needless to say, extending the knowledge of the immune-stimulating properties of aluminum-based adjuvants is of utmost importance in the development of new, safer, and efficient vaccines. To further our knowledge of the mode of action of aluminum-based adjuvants, the prospect of metabolic reprogramming of macrophages upon phagocytosis of aluminum-based adjuvants was investigated. Macrophages were differentiated and polarized in vitro from human peripheral monocytes and incubated with the aluminum-based adjuvant Alhydrogel((R)). Polarization was verified by the expression of CD markers and cytokine production. In order to recognize adjuvant-derived reprogramming, macrophages were incubated with Alhydrogel((R)) or particles of polystyrene as control, and the cellular lactate content was analyzed using a bioluminescent assay. Quiescent M0 macrophages, as well as alternatively activated M2 macrophages, exhibited increased glycolytic metabolism upon exposure to aluminum-based adjuvants, indicating a metabolic reprogramming of the cells. Phagocytosis of aluminous adjuvants could result in an intracellular depot of aluminum ions, which may induce or support a metabolic reprogramming of the macrophages. The resulting increase in inflammatory macrophages could thus prove to be an important factor in the immune-stimulating properties of aluminum-based adjuvants.

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  • 3.
    Danielsson, Ravi
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Sandberg, Tove
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Eriksson, Håkan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Aluminium Adjuvants: a Nanomaterial used as Adjuvants in Human Vaccines for Decades2018In: Open Biotechnology Journal, ISSN 1874-0707, Vol. 12, p. 140-153Article, review/survey (Refereed)
    Abstract [en]

    Background: Aluminium salts have been used for decades in vaccines as adjuvants to facilitate the adaptive immune response against co-administered antigens. Two types of aluminium adjuvant are mostly used, aluminium oxyhydroxide and aluminium hydroxyphosphate. Both types of aluminium adjuvant consist of nanoparticles that form loose, micrometre sized aggregates at circumneutral pH. Aluminium adjuvants constitute a well-documented example of administration of nanomaterials to humanswith infrequent side effects and a safety record generally regarded as excellent. However, despite its prolonged use in human and veterinary medicine, the mechanisms behind the enhanced response and the immune stimulatory effect are still by and large unknown. Methods: The present paper reviews existing ideas regarding the immunostimulatory effects of aluminium adjuvants, with a focus on the induction of an inflammatory response by cellular stress. Reviewed information was obtained from peer-reviewed scientific papers published in 1988 to date with one exception, a paper published 1931. Results: Cellular stress causes extra cellular signalling of danger associated molecular patterns (DAMPs) and upon phagocytosis of aluminium adjuvants the cells need to manage the ingested particles. Conclusion: A persistent intracellular accumulation of aluminium adjuvants will be a solid depository of sparingly soluble aluminium salts maintaining a constant concentration of Al3+ ions in the cytoplasm and this will affect multiple biochemical processes. The cell will be under constant stress and DAMP signalling will occur and we would like to suggest the maintenance of a constant concentration Al3+ ions in the cytoplasm as a general underlying feature of the immune stimulation properties of aluminium adjuvants.

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  • 4.
    Danielsson, Ravi
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Svensson, Andreas
    Falkman, Peter
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Eriksson, Håkan
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Tracing Aluminium-based Adjuvants: Their Interactions with Immune Competent Cells and their Effect on Mitochondrial Activity2018In: Open Immunology Journal, ISSN 1874-2262, Vol. 8, p. 1-15Article in journal (Refereed)
    Abstract [en]

    Background: Studies revealing the immune stimulatory properties of aluminium-based adjuvants (ABAs) have been impaired by the absence of simple and reliable methods of tracing the adjuvants and their effect on biochemical processes upon endocytosis. Objective: To verify that labelling of ABAs with lumogallion doesn’t affect the physicochemical properties of the adjuvant; tracing cellular interaction with aluminium adjuvants; explore their effect on metabolic activity upon endocytosis. Methods: Physicochemical characterization by Z-potential and size distribution of ABAs labelled with lumogallion. Cellular interactions with ABAs by flow cytometry and confocal microscopy. Metabolic activity explored by measuring transformation of tetrazolium into formazan. Results: No or minor change of zeta potential and average particle size of lumogallion labelled aluminium oxyhydroxide, AlO(OH) and aluminium hydroxyphosphate, Al(OH)x(PO4 )y. Both phagocytosing and non-phagocytosing leukocytes became associated with ABAs at concentrations expected after in vivo administration of a vaccine. The ABAs were relatively toxic, affecting both lymphocytes and monocytes, and Al(OH)x(PO4 )y was more toxic than AlO(OH). Endocytosed aluminium adjuvant particles were not secreted from the cells and remained intracellular throughout several cell divisions. The presence of ABAs increased the mitochondrial activity of the monocytic cell line THP-1 and peripheral monocytes, as based on the transformation of tetrazolium into formazan. Conclusion: Lumogallion labelled ABAs is a valuable tool tracing interactions between ABAs and cells. Labelled ABAs can be traced intracellularly and ABAs are likely to remain intracellular for a long period of time. Intracellular ABAs increase the mitochondrial activity and the presence of intracellular Al ions is suggested to cause an increased mitochondrial activity. Keywords: Aluminium based adjuvant, Lumogallion, Mitochondrial activity, MTT assay, Phagocytosis, ABAS, Zeolites.

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  • 5.
    Ohlsson, Lars
    et al.
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Hall, Anna
    Lindahl, Hanne
    Danielsson, Ravi
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Gustafsson, Anna
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV). Malmö University, Biofilms Research Center for Biointerfaces.
    Lavant, Eva
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ljunggren, Lennart
    Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Increased level of circulating cell-free mitochondrial DNA due to a single bout of strenuous physical exercise2020In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 120, p. 897-905Article in journal (Refereed)
    Abstract [en]

    Purpose Physical exercise is reported to affect the immune response in various ways. Thus, the levels of pro-inflammatory cytokines as well as the abundance of circulating leukocytes are changed. In this study, the occurence of circulating cell-free mitochondrial DNA (cfmtDNA) and nuclear DNA (nDNA) was investigated in connection with a single bout of strenuous physical exercise. Methods Healthy volunteers performed a controlled ergo-spirometry cycle test and venous blood samples were taken at different time-points to analyze the concentration of blood components before, during and after the test. The number of circulating leukocytes was measured, as well as secretion of the soluble urokinase activator receptor (suPAR). Results Cf-mtDNA significantly increased during exercise, compared to baseline values and after 30 and 90 min of rest. Circulating leukocytes increased during exercise, but returned to baseline levels afterwards. Surface expression of the urokinase plasminogen activating receptor (uPAR) on neutrophils decreased significantly during exercise. The concentration of suPAR tended to increase during exercise but only significantly after 90 min of rest. Conclusion Increased concentration of cf-mtDNA indicates that cell damage takes place during high intensity training. Hypoxia and tissue damage are likely causes of cf-mtDNA from muscle cells. The levels of cf-mtDNA remain high during the initial rest, due to the decreasing numbers of leukocytes normally clearing the plasma from cf-mtDNA. The increased levels of suPAR further emphasize that strenuous physical exercise causes a reaction similar to inflammation. Further studies are needed to detect the source of increased cf-mtDNA and the corresponding increase of suPAR liberation.

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  • 6.
    Tchekwagep, Patrick Marcel Seumo
    et al.
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Nanseu-Njiki, Charles Peguy
    Ngameni, Emmanuel
    Danielsson, Ravi
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Arnebrant, Thomas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Ruzgas, Tautgirdas
    Malmö högskola, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).
    Determination of Total Protein Concentration in Solution Using Gold Electrode Modified with Silver Nanoparticles2015In: Electroanalysis, ISSN 1040-0397, E-ISSN 1521-4109, Vol. 27, no 1, p. 253-257Article in journal (Refereed)
    Abstract [en]

    Gold electrodes were modified with silver nanoparticles and Ag/AgCl redox conversion was recorded by cyclic voltammetry in protein containing electrolyte solution. The charge of the reduction peak decreased with the increase of the total protein concentration. This correlation was better for solutions containing bovine serum albumin as a standard than for the samples of human saliva. The results of these electroanalytical measurements show that the method can be used to determine protein concentration in electrolyte solution in the range from 0.01 to 0.2 mg mL(-1), though reproducibility of analysis of real samples must be further improved.

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