title: Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products.
abstract: To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form.
authors.affiliation: Biopharmaceutical Development, MedImmune, Gaithersburg, Maryland 20878. Electronic address: IyerGowrishankaraV@MedImmune.com.
authors.forename: Vidyashankara
authors.initials: V
authors.lastname: Iyer
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Corinne
authors.initials: C
authors.lastname: Cayatte
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Marshall
authors.affiliation: Biopharmaceutical Development, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Jenny
authors.initials: J
authors.lastname: Sun
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Schneider-Ohrum
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Sean K
authors.initials: SK
authors.lastname: Maynard
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Gaurav Manohar
authors.initials: GM
authors.lastname: Rajani
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Angie Snell
authors.initials: AS
authors.lastname: Bennett
authors.affiliation: Biopharmaceutical Development, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Remmele
authors.affiliation: Biopharmaceutical Development, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Steve M
authors.initials: SM
authors.lastname: Bishop
authors.affiliation: Vaccine Platform Group, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Michael P
authors.initials: MP
authors.lastname: McCarthy
authors.affiliation: Biopharmaceutical Development, MedImmune, Gaithersburg, Maryland 20878.
authors.forename: Bilikallahalli K
authors.initials: BK
authors.lastname: Muralidhara
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004655:Emulsions / Q000737:chemistry* / Q000494:pharmacology; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000517:prevention & control; D005260:Female; D005612:Freeze Drying / Q000379:methods*; D004854:Herpesvirus 4, Human / Q000276:immunology; D007111:Immunity, Cellular; D008810:Mice, Inbred C57BL; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D013185:Squalene / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D004655:Emulsions; D014765:Viral Vaccines; D013185:Squalene
keywords: emulsion; formulation; immune response; lyophilization; vaccine adjuvants