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All vaccines are susceptible to damage by elevated temperatures and many are also damaged by freezing. The distribution, storage, and use of vaccines therefore present challenges that could be reduced by enhanced thermostability, with resulting improvements in vaccine effectiveness. Formulation and processing technologies exist that can improve the stability of vaccines at temperature extremes, however, customization is required for individual vaccines and results are variable. Considerations affecting decisions about stabilization approaches include development cost, manufacturing cost, and the ease of use of the final product. Public sector agencies can incentivize vaccine developers to prioritize stabilization efforts through advocacy and by implementing policies that increase demand for thermostable vaccines., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

All vaccines lose potency over time and the rate of potency loss is temperature-dependent. Therefore, cold-chain systems have been established to ensure that the potency of vaccines is maintained by storing them under refrigerated conditions (in most cases between 2 and 8 degrees C) until the point of use. This article aims to review the approaches being used to develop thermostable vaccine formulations that would be resistant to damage caused by freezing or excessive heat, and that could reduce dependence on the cold chain. The challenges associated with the implementation of these novel formulations are discussed, as well as the potential benefits and opportunities of taking vaccines out of the cold chain.

Vaccines containing aluminum salt adjuvants are prone to inactivation following exposure to freeze-thaw stress. Many are also prone to inactivation by heat. Thus, for maximum potency, these vaccines must be maintained at temperatures between 2 degrees C and 8 degrees C which requires the use of the cold chain. Nevertheless, the cold chain is not infallible. Vaccines are subject to freezing during both transport and storage, and frozen vaccines are discarded (under the best circumstances) or inadvertently administered despite potentially reduced potency. Here we describe an approach to minimize our reliance on the proper implementation of the cold chain to protect vaccines from freeze-thaw inactivation. By including PEG 300, propylene glycol, or glycerol in a hepatitis B vaccine, particle agglomeration, changes in the fluorescence emission spectrum--indicative of antigen tertiary structural changes--and losses of in vitro and in vivo indicators of potency were prevented following multiple exposures to -20 degrees C. The effect of propylene glycol was examined in more detail and revealed that even at concentrations too low to prevent freezing at -10 degrees C, -20 degrees C, and -80 degrees C, damage to the vaccine could be prevented. A pilot study using two commercially available diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccines suggested that the same stabilizers might protect these vaccines from freeze-thaw agglomeration as well. It remains to be determined if preventing agglomeration of DTaP vaccines preserves their antigenic activity following freeze-thaw events.

Purpose: Stable vaccines with long shelf lives and reduced dependency on the cold chain are ideal for stockpiling and rapid deployment during public emergencies, including pandemics. Spray drying is a low-cost process that has potential to produce vaccines stable at a wide range of temperatures. Our aim was to develop a stable formulation of a recombinant H1N1 influenza hemagglutinin vaccine candidate and take it to pilot-scale spray-drying production. Methods: Eight formulations containing different excipients were produced and assayed for antigen stability, powder characteristics, and immunogenicity after storage at a range of temperatures, resulting in the identification of four promising candidates. A pilot-scale spray-drying process was then developed for further testing of one formulation. Results: The pilot-scale process was used to reproducibly manufacture three batches of the selected formulation with yields >90%. All batches had stable physical properties and in vitro potency for 6 months at temperatures from −20°C to +50°C. Formulations stored for 3 months elicited immunogenic responses in mice equivalent to a frozen lot of bulk vaccine used as a stability control. Conclusions: This study demonstrates the feasibility of stabilizing subunit vaccines using a spray-drying process and the suitability of the process for manufacturing a candidate product. [ABSTRACT FROM AUTHOR]

A number of product development partnerships are actively developing new vaccines to combat infectious diseases in developing countries. To be effective, the products under development should not only be safe, efficacious, and affordable, but they should also have additional desirable technical attributes, including enhanced stability, efficient packaging, and improved ease of delivery. New technologies are now available to achieve these attributes; however, many of the technologies have yet to be adopted by the vaccine industry. This commentary discusses the opportunities and challenges associated with advancing such attributes, especially vaccine thermostability and dose sparing strategies, and the critical issues that must be addressed to bridge the gap between technology development and product development. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:29-33, 2013 [ABSTRACT FROM AUTHOR]

Aluminum-containing adjuvants have been used to enhance the immune response against killed, inactivated, and subunit antigens for more than seven decades. Nevertheless, we are only beginning to gain important insight as to what may be some very fundamental parameters for optimizing their use. For example, there is evidence that the conventional approach of maximizing antigen binding (amount and/or strength) may not result in an optimal immune response. Adsorption of antigen onto the adjuvant has recently been suggested to decrease the thermal stability of some antigens; however, whether adsorption-induced alterations to the structure and/or stability of the antigen have consequences for the elicited immune response is unclear. Finally, the thermal stability of vaccines with aluminum-containing adjuvants is not robust. Optimizing the stability of these vaccines requires an understanding of the freeze sensitivity of the adjuvant, freeze and heat sensitivity of the antigen in the presence of the adjuvant, and perhaps most important, how (or whether) various approaches to formulation can be used to address these instabilities. This review attempts to summarize recent findings regarding issues that may dictate the success of vaccines with aluminum-containing adjuvants. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:388-401, 2011 [ABSTRACT FROM AUTHOR]