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
Multiple DC responses induced by newly synthesized LDHs can be predicted with a high degree of accuracy. (a) DC responses to LiAl2-NO3 and Mg2Al-Cl were assessed as in Fig. 2. Error bars show one standard error. **, P < 0.01 versus cells alone. Four independent experiments were performed, each with three or four biological replicates. (b and c) DC responses to LiAl2-NO3 and Mg2Al-Cl were predicted with Eq. 1 following calibration of the model using data from Fig. 2. In b, the mean and 95% CIs for the measured responses are indicated (diamonds and short horizontal lines) with the predicted value (triangles) immediately below. In c, observed ln responses are shown along a straight line of gradient 1, and the predicted ln responses as squares on the same plot.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig3: Multiple DC responses induced by newly synthesized LDHs can be predicted with a high degree of accuracy. (a) DC responses to LiAl2-NO3 and Mg2Al-Cl were assessed as in Fig. 2. Error bars show one standard error. **, P < 0.01 versus cells alone. Four independent experiments were performed, each with three or four biological replicates. (b and c) DC responses to LiAl2-NO3 and Mg2Al-Cl were predicted with Eq. 1 following calibration of the model using data from Fig. 2. In b, the mean and 95% CIs for the measured responses are indicated (diamonds and short horizontal lines) with the predicted value (triangles) immediately below. In c, observed ln responses are shown along a straight line of gradient 1, and the predicted ln responses as squares on the same plot.

Mentions: We next investigated the model’s ability to predict a priori the immunological properties of newly synthesized LDHs, using the robust and relatively high-throughput DC assays we had previously used. We synthesized two new LDH compounds, LiAl2-NO3 and Mg2Al-Cl (Table S1), and made blind predictions of the multiple (n = 12) DC responses they might induce based purely on their physicochemical properties. We found the correlation between predicted and actual observed responses to be remarkably high, with a median coefficient of variation of 5.14% (Fig. 3 and Table S6). We observed that 22 of the 24 predicted values fell within the 95% confidence intervals (CIs); the probability of this occurring by chance is P < 0.0002. Conversely, just 14 out of 24 predicted values for responses elicited by one compound fall within the CIs for the responses elicited by the other, showing that the model’s predictions are composition specific. Because the predictive power of our model is proportional to the size of the datasets, its accuracy should be increased by further calibration across a wider series of LDHs with a broader range of properties.


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)

Multiple DC responses induced by newly synthesized LDHs can be predicted with a high degree of accuracy. (a) DC responses to LiAl2-NO3 and Mg2Al-Cl were assessed as in Fig. 2. Error bars show one standard error. **, P < 0.01 versus cells alone. Four independent experiments were performed, each with three or four biological replicates. (b and c) DC responses to LiAl2-NO3 and Mg2Al-Cl were predicted with Eq. 1 following calibration of the model using data from Fig. 2. In b, the mean and 95% CIs for the measured responses are indicated (diamonds and short horizontal lines) with the predicted value (triangles) immediately below. In c, observed ln responses are shown along a straight line of gradient 1, and the predicted ln responses as squares on the same plot.
© Copyright Policy - openaccess
Related In: Results  -  Collection

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

fig3: Multiple DC responses induced by newly synthesized LDHs can be predicted with a high degree of accuracy. (a) DC responses to LiAl2-NO3 and Mg2Al-Cl were assessed as in Fig. 2. Error bars show one standard error. **, P < 0.01 versus cells alone. Four independent experiments were performed, each with three or four biological replicates. (b and c) DC responses to LiAl2-NO3 and Mg2Al-Cl were predicted with Eq. 1 following calibration of the model using data from Fig. 2. In b, the mean and 95% CIs for the measured responses are indicated (diamonds and short horizontal lines) with the predicted value (triangles) immediately below. In c, observed ln responses are shown along a straight line of gradient 1, and the predicted ln responses as squares on the same plot.
Mentions: We next investigated the model’s ability to predict a priori the immunological properties of newly synthesized LDHs, using the robust and relatively high-throughput DC assays we had previously used. We synthesized two new LDH compounds, LiAl2-NO3 and Mg2Al-Cl (Table S1), and made blind predictions of the multiple (n = 12) DC responses they might induce based purely on their physicochemical properties. We found the correlation between predicted and actual observed responses to be remarkably high, with a median coefficient of variation of 5.14% (Fig. 3 and Table S6). We observed that 22 of the 24 predicted values fell within the 95% confidence intervals (CIs); the probability of this occurring by chance is P < 0.0002. Conversely, just 14 out of 24 predicted values for responses elicited by one compound fall within the CIs for the responses elicited by the other, showing that the model’s predictions are composition specific. Because the predictive power of our model is proportional to the size of the datasets, its accuracy should be increased by further calibration across a wider series of LDHs with a broader range of properties.

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