title: Stabilization of Live Attenuated Influenza Vaccines by Freeze Drying, Spray Drying, and Foam Drying.
abstract: OBJECTIVE
  The goal of this research is to develop stable formulations for live attenuated influenza vaccines (LAIV) by employing the drying methods freeze drying, spray drying, and foam drying.
  
  
  METHODS
  Formulated live attenuated Type-A H1N1 and B-strain influenza vaccines with a variety of excipient combinations were dried using one of the three drying methods. Process and storage stability at 4, 25 and 37°C of the LAIV in these formulations was monitored using a TCID50 potency assay. Their immunogenicity was also evaluated in a ferret model.
  
  
  RESULTS
  The thermal stability of H1N1 vaccine was significantly enhanced through application of unique formulation combinations and drying processes. Foam dried formulations were as much as an order of magnitude more stable than either spray dried or freeze dried formulations, while exhibiting low process loss and full retention of immunogenicity. Based on long-term stability data, foam dried formulations exhibited a shelf life at 4, 25 and 37°C of >2, 1.5 years and 4.5 months, respectively. Foam dried LAIV Type-B manufactured using the same formulation and process parameters as H1N1 were imparted with a similar level of stability.
  
  
  CONCLUSIONS
  Foam drying processing methods with appropriate selection of formulation components can produce an order of magnitude improvement in LAIV stability over other drying methods.
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Lovalenti
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Jeff
authors.initials: J
authors.lastname: Anderl
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Luisa
authors.initials: L
authors.lastname: Yee
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Van
authors.initials: V
authors.lastname: Nguyen
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Ghavami
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtake
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Saxena
authors.affiliation: SRI International, Harrisonburg, Virginia, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Voss
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, California, 95138, USA. truongv@aridispharma.com.
authors.forename: Vu
authors.initials: V
authors.lastname: Truong-Le
mesh_terms: D000818:Animals; D002460:Cell Line; D003890:Desiccation / Q000379:methods*; D004285:Dogs; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D005289:Ferrets; D005612:Freeze Drying / Q000379:methods*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000276:immunology*; D007252:Influenza Vaccines / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D029524:Betainfluenzavirus / Q000737:chemistry / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology
chemical_list: D005079:Excipients; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: Attenuated; Drying; Influenza; Stability; Vaccine
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