title: A stable live bacterial vaccine.
abstract: Formulating vaccines into a dry form enhances its thermal stability. This is critical to prevent administering damaged and ineffective vaccines, and to reduce its final cost. A number of vaccines in the market as well as those being evaluated in the clinical setting are in a dry solid state; yet none of these vaccines have achieved long-term stability at high temperatures. We used spray-drying to formulate a recombinant live attenuated Listeria monocytogenes (Lm; expressing Francisella tularensis immune protective antigen pathogenicity island protein IglC) bacterial vaccine into a thermostable dry powder using various sugars and an amino acid. Lm powder vaccine showed minimal loss in viability when stored for more than a year at ambient room temperature (∼23°C) or for 180days at 40°C. High temperature viability was achieved by maintaining an inert atmosphere in the storage container and removing oxygen free radicals that damage bacterial membranes. Further, in vitro antigenicity was confirmed by infecting a dendritic cell line with cultures derived from spray dried Lm and detection of an intracellularly expressed protective antigen. A combination of stabilizing excipients, a cost effective one-step drying process, and appropriate storage conditions could provide a viable option for producing, storing and transporting heat-sensitive vaccines, especially in regions of the world that require them the most.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Nitesh K
authors.initials: NK
authors.lastname: Kunda
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA; Department of Cell Biology and Molecular Genetics, University of Maryland, MD, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Wafula
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Meilinn
authors.initials: M
authors.lastname: Tram
authors.affiliation: Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA; Center for Infectious Disease and Immunity, University of New Mexico, Albuquerque, NM, USA.
authors.forename: Terry H
authors.initials: TH
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, USA. Electronic address: pmuttil@salud.unm.edu.
authors.forename: Pavan
authors.initials: P
authors.lastname: Muttil
mesh_terms: D001428:Bacterial Vaccines / Q000096:biosynthesis* / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology*; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011208:Powders
chemical_list: D001428:Bacterial Vaccines; D011208:Powders
keywords: Cold chain; Dry powder; Live bacterial vaccine; Spray-drying; Thermostable; Viability