Towards ambient temperature-stable vaccines: the identification of thermally stabilizing liquid formulations for measles virus using an innovative high-throughput infectivity assay

Vaccine. 2011 Jul 12;29(31):5031-9. doi: 10.1016/j.vaccine.2011.04.079. Epub 2011 May 25.

Abstract

As a result of thermal instability, some live attenuated viral (LAV) vaccines lose substantial potency from the time of manufacture to the point of administration. Developing regions lacking extensive, reliable refrigeration ("cold-chain") infrastructure are particularly vulnerable to vaccine failure, which in turn increases the burden of disease. Development of a robust, infectivity-based high throughput screening process for identifying thermostable vaccine formulations offers significant promise for vaccine development across a wide variety of LAV products. Here we describe a system that incorporates thermal stability screening into formulation design using heat labile measles virus as a prototype. The screening of >11,000 unique formulations resulted in the identification of liquid formulations with marked improvement over those used in commercial monovalent measles vaccines, with <1.0 log loss of activity after incubation for 8h at 40°C. The approach was shown to be transferable to a second unrelated virus, and therefore offers significant promise towards the optimization of formulation for LAV vaccine products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry, Pharmaceutical / methods*
  • Drug Stability
  • Excipients / chemistry
  • High-Throughput Screening Assays / methods
  • Humans
  • Measles Vaccine / chemistry*
  • Measles virus / drug effects*
  • Measles virus / pathogenicity
  • Measles virus / radiation effects*
  • Temperature

Substances

  • Excipients
  • Measles Vaccine