TY - JOUR
T1 - Long term stability of a HIV-1 neutralizing monoclonal antibody using isothermal calorimetry
AU - Clarkson, Benjamin R.
AU - Chaudhuri, Rajoshi
AU - Schön, Arne
AU - Cooper, Jonathan W.
AU - Kueltzo, Lisa
AU - Freire, Ernesto
N1 - Funding Information:
This work was supported by a grant from the National Science Foundation MCB-1157506 (EF) and by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health . We also acknowledge Jie Liu, Michael Bender, Erwin Rosales, Kandace Linkous, and Yile Li at the Vaccine Production Program for analytical support.
Funding Information:
This work was supported by a grant from the National Science Foundation MCB-1157506 (EF) and by the Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health. We also acknowledge Jie Liu, Michael Bender, Erwin Rosales, Kandace Linkous, and Yile Li at the Vaccine Production Program for analytical support.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Different factors affect the long term stability of monoclonal antibodies, among them denaturation or partial denaturation that is often followed by aggregation. Isothermal calorimetry is capable of quantifying the kinetics of denaturation/aggregation of an antibody by measuring the heat that is released or absorbed by the process over a period of days or weeks, at temperatures below its denaturation temperature, Tm. The denaturation/aggregation kinetics of the anti-HIV monoclonal antibody VRC07-523LS was measured by isothermal calorimetry at different concentrations in four different formulation buffers. The measurements were performed at ten degrees below Tm, as determined by differential scanning calorimetry. The formation of aggregates was also followed by size exclusion chromatography at 5 °C, 25 °C and 40 °C over a period of 8–36 weeks. It was observed that the rates measured by isothermal calorimetry correlate quantitatively with those measured by size exclusion chromatography. Since isothermal calorimetry experiments are performed over a period of ten days, it can become a valuable tool for a fast prediction of the best formulations.
AB - Different factors affect the long term stability of monoclonal antibodies, among them denaturation or partial denaturation that is often followed by aggregation. Isothermal calorimetry is capable of quantifying the kinetics of denaturation/aggregation of an antibody by measuring the heat that is released or absorbed by the process over a period of days or weeks, at temperatures below its denaturation temperature, Tm. The denaturation/aggregation kinetics of the anti-HIV monoclonal antibody VRC07-523LS was measured by isothermal calorimetry at different concentrations in four different formulation buffers. The measurements were performed at ten degrees below Tm, as determined by differential scanning calorimetry. The formation of aggregates was also followed by size exclusion chromatography at 5 °C, 25 °C and 40 °C over a period of 8–36 weeks. It was observed that the rates measured by isothermal calorimetry correlate quantitatively with those measured by size exclusion chromatography. Since isothermal calorimetry experiments are performed over a period of ten days, it can become a valuable tool for a fast prediction of the best formulations.
KW - Differential scanning calorimetry
KW - Isothermal calorimetry
KW - Protein denaturation
KW - Protein stability
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U2 - 10.1016/j.ab.2018.05.008
DO - 10.1016/j.ab.2018.05.008
M3 - Article
C2 - 29750942
AN - SCOPUS:85048703376
VL - 554
SP - 61
EP - 69
JO - Analytical Biochemistry
JF - Analytical Biochemistry
SN - 0003-2697
ER -