title: Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms.
abstract: Liquid chromatographic methods, combined with mass spectrometry, offer exciting and important opportunities to better characterize complex vaccine antigens including recombinant proteins, virus-like particles, inactivated viruses, polysaccharides, and protein-polysaccharide conjugates. The current abilities and limitations of these physicochemical methods to complement traditional in vitro and in vivo vaccine potency assays are explored in this review through the use of illustrative case studies. Various applications of these state-of-the art techniques are illustrated that include the analysis of influenza vaccines (inactivated whole virus and recombinant hemagglutinin), virus-like particle vaccines (human papillomavirus and hepatitis B), and polysaccharide linked to protein carrier vaccines (pneumococcal). Examples of utilizing these analytical methods to characterize vaccine antigens in the presence of adjuvants, which are often included to boost immune responses as part of the final vaccine dosage form, are also presented. Some of the challenges of using chromatographic and LC-MS as physicochemical assays to routinely test complex vaccine antigens are also discussed.
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Hickey
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Sahni
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Toth
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Ozan S
authors.initials: OS
authors.lastname: Kumru
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: Joshi
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA.
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Center, University of Kansas, Lawrence, KS 66047, USA. Electronic address: volkin@ku.edu.
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry; D000818:Animals; D000941:Antigens / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007252:Influenza Vaccines / Q000737:chemistry; D013058:Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D011994:Recombinant Proteins / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry*; D058425:Vaccines, Virus-Like Particle / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D014612:Vaccines; D058425:Vaccines, Virus-Like Particle
keywords: Adjuvant; Chromatography; Formulation; Mass spectrometry; Stability; Vaccine