Long term stability of a HIV-1 neutralizing monoclonal antibody using isothermal calorimetry

Analytical Biochemistry
Benjamin R ClarksonErnesto Freire

Abstract

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.

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Citations

Aug 11, 2018·Analytical Biochemistry·Benjamin R Clarkson, Ernesto Freire
Aug 30, 2019·Journal of Pharmaceutical Sciences·Yoann Le BasleValérie Sautou
May 12, 2021·Journal of Molecular Recognition : JMR·Robert J FalconerAnthony K Mittermaier
May 9, 2021·Analytical Biochemistry·Arne Schön, Ernesto Freire

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