VACCINE INSTABILITY IN THE COLD CHAIN: MECHANISMS, ANALYSIS AND FORMULATION STRATEGIES

Monday, 21st of July 2014 Print
[source]Vaccine[|source]

The modern vaccine formulation development path from the discovery of an immunogen to a usable vaccine includes: (1) physical and chemical characterization of the antigenic component, (2) development of stability-indicating assays including potency, (3) evaluation and optimization of the route of administration and adjuvants (in both animal models and in clinical trials), and (4) formulation design to maximize the candidate vaccines (antigen and adjuvant) stability, shelf life, and immunogenic potential. A major focus of vaccine formulation development, in many cases, is the enhancement of potency through the use of vaccine adjuvants, since many candidate immunogens fail to transfer from the laboratory to the patient due to suboptimal efficacy in humans.

In this report, the authors present a review that raises awareness about the scientific and technical challenges encountered in successfully formulating and stabilizing different types of vaccines, both in terms of stability of antigens, adjuvants and their complexes. These efforts are described in the context of maintenance of vaccine potency across the vaccine cold chain, during both clinical development and commercial distribution. More details are available at: http://www.sciencedirect.com/science/article/pii/S1045105614000487

Abstract

Instability of vaccines often emerges as a key challenge during clinical development (lab to clinic) as well as commercial distribution (factory to patient). To yield stable, efficacious vaccine dosage forms for human use, successful formulation strategies must address a combination of interrelated topics including stabilization of antigens, selection of appropriate adjuvants, and development of stability-indicating analytical methods. This review covers key concepts in understanding the causes and mechanisms of vaccine instability including (1) the complex and delicate nature of antigen structures (e.g., viruses, proteins, carbohydrates, protein-carbohydrate conjugates, etc.), (2) use of adjuvants to further enhance immune responses, (3) development of physicochemical and biological assays to assess vaccine integrity and potency, and (4) stabilization strategies to protect vaccine antigens and adjuvants (and their interactions) during storage. Despite these challenges, vaccines can usually be sufficiently stabilized for use as medicines through a combination of formulation approaches combined with maintenance of an efficient cold chain (manufacturing, distribution, storage and administration). Several illustrative case studies are described regarding mechanisms of vaccine instability along with formulation approaches for stabilization within the vaccine cold chain. These include live, attenuated (measles, polio) and inactivated (influenza, polio) viral vaccines as well as recombinant protein (hepatitis B) vaccines.

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