Challenges and opportunities of using liquid chromatography and mass spectrometry methods to develop complex vaccine antigens as pharmaceutical dosage forms

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2016-10, Vol.1032, p.23-38
• Main Authors: Hickey, John M., Sahni, Neha, Toth, Ronald T., Kumru, Ozan S., Joshi, Sangeeta B., Middaugh, C. Russell, Volkin, David B.
• Format: Article
• Language: English
• Subjects: Adjuvant; Adjuvants, Immunologic - chemistry; Animals; Antigens - chemistry; Chromatography; Chromatography, Liquid - instrumentation; Chromatography, Liquid - methods; Formulation; Humans; Influenza Vaccines - chemistry; Mass spectrometry; Mass Spectrometry - instrumentation; Mass Spectrometry - methods; Recombinant Proteins - chemistry; Stability; Vaccine; Vaccines - chemistry; Vaccines, Virus-Like Particle - chemistry
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2016.04.001

•High-resolution analytical methods are critical to develop complex vaccine antigens.•Liquid chromatographic and mass spectrometric methods are reviewed.•Some of the advantages and challenges of using these methods are also discussed. 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.