title: Screening vaccine formulations for biological activity using fresh human whole blood.
abstract: Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Roger H
authors.initials: RH
authors.lastname: Brookes
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Jalil
authors.initials: J
authors.lastname: Hakimi
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Yukyung
authors.initials: Y
authors.lastname: Ha
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Aboutorabian
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Salvador F
authors.initials: SF
authors.lastname: Ausar
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Manvi
authors.initials: M
authors.lastname: Hasija
authors.affiliation: Faculty of Infectious and Tropical Diseases; Department of Immunology and Infection; London School of Hygiene and Tropical Medicine; London, UK.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Applied Sciences; Faculty of Health & Life Sciences; Northumbria University; Newcastle upon Tyne, UK.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Todryk
authors.affiliation: Faculty of Infectious and Tropical Diseases; Department of Immunology and Infection; London School of Hygiene and Tropical Medicine; London, UK.
authors.forename: Hazel M
authors.initials: HM
authors.lastname: Dockrell
authors.affiliation: Department of Bioprocess Research and Development; Formulation and Stability Platform; Sanofi Pasteur; Toronto, ON Canada.
authors.forename: Nausheen
authors.initials: N
authors.lastname: Rahman
mesh_terms: D001769:Blood / Q000276:immunology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D006801:Humans; D014612:Vaccines / Q000276:immunology*
chemical_list: D014612:Vaccines
keywords: WBA; adjuvant modulation,vaccine; functionality; tuberculosis