title: Development of a highly thermostable, adjuvanted human papillomavirus vaccine.
abstract: 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 HPV16 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°C for 12weeks, 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®, 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.
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, United States.
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Hassett
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, United States; The Bio Frontiers Institute, University of Colorado, Boulder, CO 80309, United States.
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Meinerz
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, United States.
authors.forename: Florian
authors.initials: F
authors.lastname: Semmelmann
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, United States.
authors.forename: Megan C
authors.initials: MC
authors.lastname: Cousins
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, United States; The Bio Frontiers Institute, University of Colorado, Boulder, CO 80309, United States.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Garcea
authors.affiliation: Center for Pharmaceutical Biotechnology, Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, United States. Electronic address: Theodore.randolph@colorado.edu.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Randolph
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002152:Calorimetry, Differential Scanning; D036022:Capsid Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004356:Drug Storage; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005612:Freeze Drying; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D053918:Papillomavirus Vaccines / Q000737:chemistry* / Q000276:immunology*; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; C114580:HPV L1 protein, Human papillomavirus; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; C510352:human papillomavirus vaccine, L1 type 16, 18
keywords: Aluminum hydroxide; Glycopyranoside lipid A; Human papillomavirus; Lyophilization; Stability; Vaccine