Development of a highly thermostable, adjuvanted human papillomavirus vaccine

A major impediment to economical, worldwide vaccine distribution is the requirement for a "cold chain" to preserve antigenicity. We addressed this problem using a model human papillomavirus (HPV) vaccine stabilized by immobilizing HPVI 6 L1 capsomeres, i.e., pentameric subunits of the virus capsid, within organic glasses formed by lyophilization. Lyophilized glass and liquid vaccine formulations were incubated at 50 degrees C 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. Capsomeres in glassy-state vaccines retained tertiary and quaternary structure, and critical conformational epitopes. Moreover, glassy formulations adjuvanted with aluminum hydroxide or aluminum hydroxide and glycopyranoside lipid A were not only as immunogenic as the commercially available HPV vaccine Cervarix (R), but also retained complete neutralizing immunogenicity after high-temperature storage. The thermal stability of such adjuvanted vaccine powder preparations may thus eliminate the need for the cold chain. (C) 2015 Elsevier B.V. All rights reserved.