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

• Published in: Vaccine Vol. 29; no. 31; pp. 5031 - 5039
• Main Authors: Schlehuber, Lisa D, McFadyen, Iain J, Shu, Yu, Carignan, James, Duprex, W. Paul, Forsyth, William R, Ho, Jason H, Kitsos, Christine M, Lee, George Y, Levinson, Douglas A, Lucier, Sarah C, Moore, Christopher B, Nguyen, Niem T, Ramos, Josephine, Weinstock, B. André, Zhang, Junhong, Monagle, Julie A, Gardner, Colin R, Alvarez, Juan C
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 12.07.2011; Elsevier; Elsevier Limited
• Subjects: Allergy and Immunology; Ambient temperature; Applied microbiology; Biological and medical sciences; burden of disease; Chemistry, Pharmaceutical - methods; Cold; Cold-chain; Drug Stability; Excipients - chemistry; Formulation; Fundamental and applied biological sciences. Psychology; Gates Foundation Grand Challenges in Global Health; heat; High-throughput; High-Throughput Screening Assays - methods; Human viral diseases; Humans; Immunization; Infectious diseases; infrastructure; manufacturing; Measles; Measles Vaccine - chemistry; Measles virus; Measles virus - drug effects; Measles virus - pathogenicity; Measles virus - radiation effects; Medical sciences; Microbiology; Miscellaneous; pathogenicity; Pharmaceutical industry; Refrigeration; screening; Temperature; thermal stability; Thermostability; vaccine development; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral diseases; Viral diseases with cutaneous or mucosal lesions and viral diseases of the eye; Virology; viruses; Thermostability; High-throughput; Cold-chain; Gates Foundation Grand Challenges in Global Health; Measles; Formulation; Gates Foundation Grand Challenges in; Temperature; Global Health; Identification; Vaccine; Thermal stability; Paramyxoviridae; Infection; Virus; Paramyxovirinae; Mononegavirales; Viral disease; Infectivity; Morbillivirus; Measles virus
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.04.079

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 <1.0log 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.