Stabilization of measles virus for vaccine formulation.
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.
Kissmann
Julian
J
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Ausar
Salvador F
SF
Rudolph
Angela
A
Braun
Chad
C
Cape
Stephen P
SP
Sievers
Robert E
RE
Federspiel
Mark J
MJ
Joshi
Sangeeta B
SB
Middaugh
C Russell
CR
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
D005079:Excipients; D008458:Measles Vaccine; D014613:Vaccines, Attenuated