Capsomeres in glassy-state vaccines retained tertiary and quaternary structure, and critical conformational epitopes. Lyophilized glass and liquid vaccine formulations were incubated at 50☌ for 12 weeks, and then analyzed for retention of capsomere conformational integrity and the ability to elicit neutralizing antibody responses after immunization of BALB/c mice.
We addressed this problem using a model human papillomavirus (HPV) vaccine stabilized by immobilizing HPV16 L1 capsomeres, i.e., pentameric subunits of the virus capsid, within organic glasses formed by lyophilization.
and the American Pharmacists Association J Pharm SciĪ major impediment to economical, worldwide vaccine distribution is the requirement for a "cold chain" to preserve antigenicity. Vaccines containing aluminum hydroxide and GLA elicited higher immune responses than vaccines adjuvanted with only aluminum hydroxide, with more mice responding to a single dose. In contrast, upon lyophilization, no additional deamidation after 4 weeks at 40☌ and no detectable changes in DNI structure or reduction in immunogenicity after 16 weeks at 40☌ were observed. Concomitant with efficacy losses at elevated temperatures, changes in DNI structure were detected by fluorescence spectroscopy and increased deamidation was observed by capillary isoelectric focusing (cIEF) after only 1 week of storage of the liquid formulation at 40☌.
Immunogenicity of liquid vaccines also decreased when stored at 40☌ for 8 weeks, as measured by decreases in neutralizing antibody titers in vaccinated mice. Freeze–thawing of the liquid vaccine caused the adjuvants to aggregate and decreased its immunogenicity in mice. To better understand and prevent such losses, dominant negative inhibitor (DNI), a recombinant protein antigen for a candidate vaccine against anthrax, was formulated as a liquid and as a glassy lyophilized powder with the adjuvants aluminum hydroxide and glycopyranoside lipid A (GLA).
During transport and storage, vaccines may be exposed to temperatures outside of the range recommended for storage, potentially causing efficacy losses.
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