title: Long-term thermostabilization of live poxviral and adenoviral vaccine vectors at supraphysiological temperatures in carbohydrate glass.
abstract: Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors-E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara-in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45 degrees C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector-based biopharmaceuticals in resource-poor settings.
authors.affiliation: Cambridge Biostability Ltd., Cambridge Science Park, Milton Road, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Alcock
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Cottingham
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rollier
authors.forename: Julie
authors.initials: J
authors.lastname: Furze
authors.forename: Samodh D
authors.initials: SD
authors.lastname: De Costa
authors.forename: Marian
authors.initials: M
authors.lastname: Hanlon
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: Spencer
authors.forename: Jared D
authors.initials: JD
authors.lastname: Honeycutt
authors.forename: David H
authors.initials: DH
authors.lastname: Wyllie
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Migena
authors.initials: M
authors.lastname: Bregu
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D002241:Carbohydrates / Q000737:chemistry*; D004356:Drug Storage / Q000379:methods*; D005822:Genetic Vectors; D005898:Glass / Q000737:chemistry; D006801:Humans; D013395:Sucrose / Q000737:chemistry; D014199:Trehalose / Q000737:chemistry; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000378:metabolism*
chemical_list: D002241:Carbohydrates; D014765:Viral Vaccines; D013395:Sucrose; D014199:Trehalose