Factors influencing the stability of live oral attenuated bacterial vaccines.

Live oral attenuated vaccines against typhoid fever (Salmonella typhi Ty21a) and cholera (Vibrio cholerae CVD 103-HgR) have been licensed for human use. Vaccine potency is dependent upon each dose containing a minimum number of viable organisms and galenic parameters. To ensure long-term stability, such vaccines must be stored at 5 degrees C +/- 3 degrees C. However, exposure to ambient temperatures (25 degrees C) for short periods of time (< 7 days) does not compromise vaccine potency. Brief exposures (< or = 24 hours) to temperatures as high as 37 degrees C will also not render the vaccine unsuitable for use. The Ty21a vaccine is available either as enteric-coated capsules or as a "liquid formulation", while CVD 103-HgR is presented only in the latter form. Each galenic formulation presents unique challenges with regard to the production of stable vaccines. Residual moisture, excipients, and processing temperatures during manufacturing were all found to markedly affect vaccine stability.