Rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine.

Deamidation of the recombinant protective antigen (rPA) correlates with decreased effectiveness of the vaccine in protecting against infection by Bacillus anthracis. We present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rPA adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rPA stored in solution without adjuvant. Although deamidation did not impact total levels of rPA-specific antibodies in a mouse model, it did correlate with a decrease in toxin-neutralizing antibodies.

Evaluation of the effect of syringe surfaces on protein formulations.

Packaging of drugs in prefillable syringes offers considerable advantages over conventional vials. Almost all major biotech molecules are available on the market today in prefilled syringes, and are safe and efficacious. Newer high-concentration liquid formulations, especially fusion proteins, however, can suffer from instability in prefilled syringes due to syringe components like silicone oil.

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection.

Biophysical characterization and formulation of F1-V, a recombinant plague antigen.

The recombinant plague antigen, F1-V, was studied for its structural characteristics using several biophysical techniques. A larger apparent molecular weight relative to its calculated molecular weight obtained from size exclusion chromatography, an unusually large R(g) obtained from MALS, and ANS dye binding studies which indicate that all hydrophobic regions of the protein are exposed to solvent demonstrated that F1-V exists like a disordered protein with a worm-like conformation. The pH-solubility profile of F1-V showed a solubility minimum at pH 5, close to its pI, consistent with the lack of repulsive forces that result in aggregation.

Noninvasive delivery technologies: respiratory delivery of vaccines.

This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements.

Anthrax vaccine powder formulations for nasal mucosal delivery.

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation.