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Clin Vaccine Immunol 2009 Jul;16(7):1025-32

The Development of a Murine Mycobacterial Growth Inhibition Assay for Evaluating Vaccines Against Mycobacterium tuberculosis.

Parra M, Yang AL, Lim J, Kolibab K, Derrick S, Cadieux N, Perera LP, Jacobs WR, Brennan M, Morris SL


The development and characterization of new tuberculosis vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of M. tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a MVA construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth inhibitory responses seen in vitro after one week of co-culture correlate with the protective immune responses detected in vivo at 28 days post-challenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently up-regulated cytokines detected in the immune co-cultures are IFN-gamma, growth differentiation factor -15 (GDF-15), IL-21, IL-27, and TNF-alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues including product potency and stability.

Category: Journal Article
PubMed ID: #19458207 DOI: 10.1128/CVI.00067-09
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29