An in vitro functional assay to measure the biological activity of TB vaccine candidate H4-IC31.

Autor: Ming M; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada. Electronic address: Marin.Ming@sanofi.com., Bernardo L; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Williams K; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Kolattukudy P; University of Central Florida, Burnett School of Biomedical Science, 6900 Lake Nona Blvd, Orlando, USA., Kapoor N; University of Central Florida, Burnett School of Biomedical Science, 6900 Lake Nona Blvd, Orlando, USA., Chan LG; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Pagnon A; Sanofi Pasteur, Research Department, 1541, Avenue Marcel Mérieux, Marcy l'Etoile, France., Piras F; Sanofi Pasteur, Research Department, 1541, Avenue Marcel Mérieux, Marcy l'Etoile, France., Su J; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Gajewska B; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Salha D; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada., Gisonni-Lex L; Sanofi Pasteur, Analytical Sciences, 1755 Steeles Avenue West, Toronto, Canada.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2019 May 16; Vol. 37 (22), pp. 2960-2966. Date of Electronic Publication: 2019 Apr 19.
DOI: 10.1016/j.vaccine.2019.04.035
Abstrakt: Potency assays for vaccine products are an important regulatory requirement, and are used to assess product quality and consistency prior to lot release for clinical testing. Ideally they measure an established correlate of efficacy or protection. In cases where there is no known correlate of protection, however, a functional assay that measures a biological response to a vaccine can be applied as a potency assay. Here we describe an in vitro assay which quantitatively measures human T cell activation as a biological response to the TB vaccine candidate H4-IC31. The Cytokine Secretion Assay (CSA) is based on the ability of peripheral blood mononuclear cells (PBMCs) from a Bacillus Calmette-Guérin (BCG)-vaccinated human donor to process and respond to H4-IC31. The ability of H4-IC31 to stimulate a cellular immune response is measured through the quantification of secreted IFNγ and is reported as relative stimulatory activity (RSA) compared to an in-house reference standard. The CSA is specific to the H4-IC31 vaccine, determines the RSA of H4-IC31 in the range of 50% to 150% of the reference standard, and is stability indicating as it detects differences in RSA between intact and heat treated H4-IC31. Although the CSA does not provide a link to clinical efficacy, it fulfills the critical requirements for a biological potency test to assess TB vaccine candidates and can be used along with biochemical and immunochemical assays to define a product profile during clinical development, while eliminating the use of animals for product testing.
(Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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