Limits...
Immunity induced by a broad class of inorganic crystalline materials is directly controlled by their chemistry.

Williams GR, Fierens K, Preston SG, Lunn D, Rysnik O, De Prijck S, Kool M, Buckley HC, Lambrecht BN, O'Hare D, Austyn JM - J. Exp. Med. (2014)

Bottom Line: Using a systems vaccinology approach, we find that every measured response can be modeled using a subset of just three physical and chemical properties for all compounds tested.This correlation can be reduced to a simple linear equation that enables the immunological responses stimulated by newly synthesized LDHs to be predicted in advance from these three parameters alone.This study demonstrates that immunity can be determined purely by chemistry and opens the possibility of rational manipulation of immunity for therapeutic purposes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UKChemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.

Show MeSH

Related in: MedlinePlus

Illustrations of typical LDHs and the systems vaccinology approach used in this study. (a–e) Transmission electron micrographs of LiAl2-CO3 (a), Mg2Al-NO3 (b), Mg2Fe-Cl (c), Imject alum (d), and Alhydrogel (e). Size data on the LDHs are in Table S1. (f) A schematic showing the systems vaccinology approach. To the left, the general LDH structure is depicted, showing the positively charged layers (yellow/blue/red circles) and interlayer anions (green circles), with a surrounding layer of water (top and bottom). The in vitro DCs and in vivo antibody responses stimulated by a series of LDHs were evaluated, and the datasets were then independently subjected to multivariate analysis, with the physicochemical properties of LDHs detailed in Table S4. All observed responses were highly correlated with the three key physicochemical properties indicated on the left side and conformed to the equation (Eq. 1) illustrated on the right side. This equation was then used to predict, de novo, the immunological (DC) responses stimulated by newly synthesized LDHs from their respective physicochemical properties.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4042647&req=5

fig1: Illustrations of typical LDHs and the systems vaccinology approach used in this study. (a–e) Transmission electron micrographs of LiAl2-CO3 (a), Mg2Al-NO3 (b), Mg2Fe-Cl (c), Imject alum (d), and Alhydrogel (e). Size data on the LDHs are in Table S1. (f) A schematic showing the systems vaccinology approach. To the left, the general LDH structure is depicted, showing the positively charged layers (yellow/blue/red circles) and interlayer anions (green circles), with a surrounding layer of water (top and bottom). The in vitro DCs and in vivo antibody responses stimulated by a series of LDHs were evaluated, and the datasets were then independently subjected to multivariate analysis, with the physicochemical properties of LDHs detailed in Table S4. All observed responses were highly correlated with the three key physicochemical properties indicated on the left side and conformed to the equation (Eq. 1) illustrated on the right side. This equation was then used to predict, de novo, the immunological (DC) responses stimulated by newly synthesized LDHs from their respective physicochemical properties.

Mentions: Through their capacity to elicit danger signals, alums have for many decades been incorporated into vaccines to stimulate high levels of protective antibodies against the antigens they contain (Marrack et al., 2009; Coffman et al., 2010). The alum used as adjuvants usually comprises aluminum oxyhydroxide (AlOOH) or aluminum hydroxyphosphate (Al(OH)x(PO4)y), but the materials are heterogeneous and poorly characterized. In contrast, layered double hydroxides (LDHs) are structurally and chemically homogeneous crystalline materials represented by the general chemical formula [Mz+1−xM3+x(OH)2]p+(Xn−)p/n·yH2O (see Fig. 1). In essence, the structure is a sandwich of positively charged mixed-metal hydroxide layers (containing both a trivalent [M3+] and either a monovalent [M+] or divalent [M2+] cation) with interlayers of negatively charged anions. LDHs can be synthesized in thousands of different chemical compositions with a large range of possible metal cations, varied ratios of (M+/M2+):M3+, and many different anions. Because alums are solid, ionic hydroxyl salts, we reasoned that LDHs may also elicit immunological responses; if so, the versatility of these materials would enable us to explore the impact of systematic chemical substitutions on the types of immunity induced.


Immunity induced by a broad class of inorganic crystalline materials is directly controlled by their chemistry.

Williams GR, Fierens K, Preston SG, Lunn D, Rysnik O, De Prijck S, Kool M, Buckley HC, Lambrecht BN, O'Hare D, Austyn JM - J. Exp. Med. (2014)

Illustrations of typical LDHs and the systems vaccinology approach used in this study. (a–e) Transmission electron micrographs of LiAl2-CO3 (a), Mg2Al-NO3 (b), Mg2Fe-Cl (c), Imject alum (d), and Alhydrogel (e). Size data on the LDHs are in Table S1. (f) A schematic showing the systems vaccinology approach. To the left, the general LDH structure is depicted, showing the positively charged layers (yellow/blue/red circles) and interlayer anions (green circles), with a surrounding layer of water (top and bottom). The in vitro DCs and in vivo antibody responses stimulated by a series of LDHs were evaluated, and the datasets were then independently subjected to multivariate analysis, with the physicochemical properties of LDHs detailed in Table S4. All observed responses were highly correlated with the three key physicochemical properties indicated on the left side and conformed to the equation (Eq. 1) illustrated on the right side. This equation was then used to predict, de novo, the immunological (DC) responses stimulated by newly synthesized LDHs from their respective physicochemical properties.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4042647&req=5

fig1: Illustrations of typical LDHs and the systems vaccinology approach used in this study. (a–e) Transmission electron micrographs of LiAl2-CO3 (a), Mg2Al-NO3 (b), Mg2Fe-Cl (c), Imject alum (d), and Alhydrogel (e). Size data on the LDHs are in Table S1. (f) A schematic showing the systems vaccinology approach. To the left, the general LDH structure is depicted, showing the positively charged layers (yellow/blue/red circles) and interlayer anions (green circles), with a surrounding layer of water (top and bottom). The in vitro DCs and in vivo antibody responses stimulated by a series of LDHs were evaluated, and the datasets were then independently subjected to multivariate analysis, with the physicochemical properties of LDHs detailed in Table S4. All observed responses were highly correlated with the three key physicochemical properties indicated on the left side and conformed to the equation (Eq. 1) illustrated on the right side. This equation was then used to predict, de novo, the immunological (DC) responses stimulated by newly synthesized LDHs from their respective physicochemical properties.
Mentions: Through their capacity to elicit danger signals, alums have for many decades been incorporated into vaccines to stimulate high levels of protective antibodies against the antigens they contain (Marrack et al., 2009; Coffman et al., 2010). The alum used as adjuvants usually comprises aluminum oxyhydroxide (AlOOH) or aluminum hydroxyphosphate (Al(OH)x(PO4)y), but the materials are heterogeneous and poorly characterized. In contrast, layered double hydroxides (LDHs) are structurally and chemically homogeneous crystalline materials represented by the general chemical formula [Mz+1−xM3+x(OH)2]p+(Xn−)p/n·yH2O (see Fig. 1). In essence, the structure is a sandwich of positively charged mixed-metal hydroxide layers (containing both a trivalent [M3+] and either a monovalent [M+] or divalent [M2+] cation) with interlayers of negatively charged anions. LDHs can be synthesized in thousands of different chemical compositions with a large range of possible metal cations, varied ratios of (M+/M2+):M3+, and many different anions. Because alums are solid, ionic hydroxyl salts, we reasoned that LDHs may also elicit immunological responses; if so, the versatility of these materials would enable us to explore the impact of systematic chemical substitutions on the types of immunity induced.

Bottom Line: Using a systems vaccinology approach, we find that every measured response can be modeled using a subset of just three physical and chemical properties for all compounds tested.This correlation can be reduced to a simple linear equation that enables the immunological responses stimulated by newly synthesized LDHs to be predicted in advance from these three parameters alone.This study demonstrates that immunity can be determined purely by chemistry and opens the possibility of rational manipulation of immunity for therapeutic purposes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Chemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UKChemistry Research Laboratory, Department of Chemistry; Nuffield Department of Surgical Sciences, John Radcliffe Hospital; and Department of Statistics; University of Oxford, Oxford OX1 2JD, England, UK.

Show MeSH
Related in: MedlinePlus