Vaccines with aluminum-containing adjuvants: optimizing vaccine efficacy and thermal stability.

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.

A heat-stable hepatitis B vaccine formulation.

The purpose of the present study was to develop a formulation of recombinant hepatitis B vaccine with improved stability at elevated temperatures. A validated in vitro antigen reactivity assay was used to measure the stability of the vaccine. The formulation development focused on modification of the interactions between the antigen and aluminum hydroxide adjuvant and subsequent optimization of the ionic aqueous environment of the adsorbed vaccine. A formulation of hepatitis B vaccine containing 40 mM histidine and 40 mM phosphate at pH 5.2 had considerably improved stability at elevated temperatures as measured by the in vitro antigen reactivity assay. The formulation exhibited 9-week stability at 55 degrees C and was subsequently shown to be stable both at 37 degrees C and at 45 degrees C for at least 6 months based on the in vitro antigen reactivity and immunogenicity in mice. The formulation comprises only excipients which have a history of safe use in approved drug products. The new vaccine formulation has the potential to be used outside the cold chain for part of its shelf life. This may improve the immunization coverage, simplify the logistics for outreach immunization, and ensure the potency of the vaccine in areas where the cold chain is insufficient.