Date of Award

Summer 7-17-2014

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Theodore W. Randolph

Second Advisor

John F. Carpenter

Third Advisor

Joel L. Kaar

Abstract

Vaccines often require a narrow temperature range for storage during the cold chain. Damage to vaccines can occur if the vaccines are frozen, or exposed to elevated temperatures which could ultimately lead to a loss in vaccine efficacy. Lyophilized vaccines allow for a wider range of storage temperatures without having vaccines experience a decrease in efficacy. By utilizing rapid freezing kinetics and high concentrations of the glass-forming excipient trehalose, the particle size distribution of aluminum hydroxide adjuvant particles was maintained during lyophilization and reconstitution. Lyophilized recombinant ricin toxin A, dominant negative inhibitor, and human papillomavirus vaccines were equally as immunogenic as their liquid counterparts. The lyophilized vaccines were able to remain stable without protein structural changes or a decrease in immunogenicity after storage at an elevated temperature of 40-50 ºC, where liquid vaccines exhibited alterations in protein antigen structure and decreased immunogenicity. The addition of the tolllike receptor agonist, glycopyranoside lipid A was able to increase antibody titers and the rate of seroconversion for the anthrax vaccines but failed to do so for the human papillomavirus vaccines, showing that the immune response may be antigen specific. Although, no commercially available vaccines are lyophilized in the presence of an aluminum salt adjuvant, the work presented in this thesis provide evidence that lyophilization can be used successfully with aluminum hydroxide and glycopyranoside lipid A adjuvants.

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