TOWARDS AMBIENT TEMPERATURE-STABLE VACCINES: THE IDENTIFICATION OF THERMALLY STABILIZING LIQUID FORMULATIONS FOR MEASLES VIRUS USING AN INNOVATIVE HIGH-THROUGHPUT INFECTIVITY ASSAY

Monday, 21st of July 2014

[source]Vaccine[|source]

Measles Vaccine (MV) is inherently labile, losing 50% potency after 1 h at 22–25 °C and almost 100% after 1 h at 37 °C. Reducing the moisture content in the vaccine, most commonly through lyophilization, or alternatively through spray drying, can lead to dramatic improvements in the stability of the vaccine during storage and distribution; however, reconstitution prior to vaccination is still required.  Improvement in the stability of liquid (reconstituted) measles vaccine at ambient temperatures could deliver significant value in the developing world, where multi-dose vials are still used.

 In this report, the authors describe the development of a high throughput (HT) screening platform capable of simultaneously evaluating the thermostability performance for hundreds of MV formulations. The authors identified multiple formulations capable of maintaining the potency of the vaccine in the liquid state at 40 °C for at least 8 h. The report suggests that these formulations may offer increased thermal stability for a monovalent measles vaccine when compared to currently marketed products, and in some cases also offer a cost benefit and eliminate the need for animal-derived components. More details are accessible at: http://www.sciencedirect.com/science/article/pii/S0264410X11006347

 

 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 8 h 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.