title: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Kissmann
authors.forename: Salvador F
authors.initials: SF
authors.lastname: Ausar
authors.forename: Angela
authors.initials: A
authors.lastname: Rudolph
authors.forename: Chad
authors.initials: C
authors.lastname: Braun
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Cape
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: Joshi
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
mesh_terms: D002942:Circular Dichroism; D004355:Drug Stability; D005079:Excipients; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008458:Measles Vaccine / Q000737:chemistry*; D008459:Measles virus / Q000502:physiology* / Q000648:ultrastructure; D013057:Spectrum Analysis; D013696:Temperature; D014613:Vaccines, Attenuated / Q000737:chemistry
chemical_list: D005079:Excipients; D008458:Measles Vaccine; D014613:Vaccines, Attenuated