Formulation approach for the development of a stable, lyophilized formaldehyde-containing vaccine.

Formaldehyde has been used in the inactivation of a number of viral and bacterial toxins used in vaccines. In some cases, a small amount of formaldehyde may be necessary in order to prevent reversion back to the toxic state during storage. When a lyophilized preparation is required, care must be taken to ensure that formaldehyde is not lost during the process in order to ensure safety of the product.

Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.

The mechanism(s) of the enhancement of the immune response by addition of aluminum salt adjuvants to parenterally administered protein-based vaccines is still the subject of debate. It has been hypothesized, however, that destabilization of the antigen structure on the surface of the adjuvant may be important for eliciting immune response. Also, it has been suggested that immune response to adjuvanted vaccines is reduced if the adjuvant particles become aggregated before administration because of processing steps such as freeze-drying.

Influence of particle size and antigen binding on effectiveness of aluminum salt adjuvants in a model lysozyme vaccine.

It has been suggested that agglomeration of aluminum salt adjuvant particles during freezing and drying can cause loss of immunogenicity of vaccines formulated with such adjuvants. In this study, we tested this hypothesis and examined the immune response in a murine model to various liquid, freeze-thawed, and lyophilized vaccine formulations, using lysozyme as a model antigen. The various processing techniques and excipient levels resulted in a wide range of particle size distributions (PSDs) and antigen-adjuvant binding levels.

Inhibition of aggregation of aluminum hydroxide adjuvant during freezing and drying.

Aluminum-salt adjuvants are widely used to increase immunogenicity of recombinant protein vaccines. However, when vaccines formulated with these adjuvants are frozen or lyophilized, losses of efficacy are often reported. This loss of potency is usually attributed to the aggregation of adjuvant particles during processing.