Stabilization of measles virus for vaccine formulation

Abstract

An attenuated live measles virus (MV) was characterized by several biophysical methods as a function of temperature and pH. Following a method developed previously, the resultant light scattering and spectroscopic data were synthesized into an empirical phase diagram that visually and simultaneously represents the entire data set. Using this empirically-based phase diagram, screening assays were developed to identify potential vaccine stabilizers. Various compounds are shown by these assays to inhibit the temperature-induced aggregation of viral particles, and also to protect the integrity of the viral envelope. Accelerated stability assays show that, upon thermal challenge, MV formulated with these excipients retains its infectivity to a significant extent. Thus, the enhanced physical stability produced by this method is shown to protect the biological activity of this important but labile vaccine.

Towards development of stable formulations of a live attenuated bacterial vaccine: A preformulation study facilitated by a biophysical approach

“…This, in turn, can be used to determine the optimal conditions for trial formulations and high throughput excipient screening assays. 13,[18][19][20][21][31][32][33] The present research expands the application of EPDs to a more complex and heterogeneous system than those that have been previously studied. The EPD of Ty21a cells clearly indicates that the cells are most stable at pH 6 to 7 and at temperatures below 30°C.…”

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

“…herpesvirus particles, are sensitive towards heat [46,47], low pH and low osmolality [48,49]. The stability of some enveloped viruses against inactivation due to temperature or osmolality effects can be increased by adding stabilizer to the culture medium such as sucrose, glycerol, trehalose or a compatible solute [50][51][52].…”

A Rational, Systematic Approach for the Development of Vaccine Formulations

“…Unfolding of the antigen is indicated by a blue shift in the wavelength of the absorbance peak minima while aggregation is indicated with a red shift in the peak minima phase diagram of pH versus temperature can be constructed from these color vectors (Fig. 3) (12), bacterial (13), as well as sub-unit (14,15) vaccine antigens and is a valuable tool for selection of appropriate pH conditions early in development.…”

“…Excipient screening such as monitoring of optical density or extrinsic fluorescence can be performed in a 96 well format to allow high-throughput screening of many excipients and excipient combinations at one time. This is a powerful approach to obtain a large quantity of stability data quickly and has been used in the development of C. difficile (16,17), Bacillus anthracis (14), measles (12), hepatitis (18), as well as other vaccines. Once the pH, buffer, and stabilizer(s) have been determined, focus of development can shift towards understanding how environmental stresses such as low or high temperatures as well as incorporation of adjuvants to enhance immunogenicity may impact antigen stability.…”