Assessment of vaccine testing at three laboratories using the guinea pig model of tuberculosis

Abstract

The guinea pig model of tuberculosis is used extensively in different locations to assess the efficacy of novel tuberculosis vaccines during pre-clinical development. Two key assays are used to measure protection against virulent challenge: a 30 day post-infection assessment of mycobacterial burden and long term post-infection survival and pathology analysis. To determine the consistency and robustness of the guinea pig model for testing vaccines, a comparative assessment between three sites that are currently involved in testing tuberculosis vaccines from external providers was performed. Each site was asked to test two “subunit” type vaccines in their routine animal model as if testing vaccines from a provider. All sites performed a 30 day study, and one site also performed a long-term survival/pathology study. Despite some differences in experimental approach between the sites, such as the origin of the M. tuberculosis strain and the type of aerosol exposure device used to infect the animals and the source of the guinea pigs, the data obtained between sites were consistent in regard to the ability of each “vaccine” tested to reduce the mycobacterial burden. The observations also showed that there was good concurrence between the results of short-term and long-term studies. This validation exercise means that efficacy data can be compared between sites.

Animal Models of Tuberculosis: Guinea Pigs

“…Unsensitized animals infected with less than five bacilli succumbed to disease from week 14 postchallenge, but even after 40 wk, 20% of the animals had survived (Wiegeshaus et al 1970). In contrast, studies performed more recently generally use aerosol doses of 20 -50 bacilli and, even though this is still regarded as low-dose, the progression to severe disease is more rapid and 100% of animals have met humane end points by week 30 (Brandt et al 2004;Williams et al 2009;Grover et al 2012). Even higher aerosol doses ( 500-1000) have been used, which result in accelerated times to humane end points of between 8 and 20 wk.…”

Domestic Animal Models for Biomedical Research

“…Vaccine testing in guinea pig tuberculosis models (Obregon‐Henao et al. 2011) is an important part of this field and has been reviewed elsewhere (Grover et al. 2012).…”

“…The widest application of such models can be found in tuberculosis research (Dharmadhikari and Nardell 2008). Vaccine testing in guinea pig tuberculosis models (Obregon-Henao et al 2011) is an important part of this field and has been reviewed elsewhere (Grover et al 2012). They have also provided novel insight into the mechanisms of infection such as the metabolic changes that occur in infected tissues (Somashekar et al 2011).…”

Kinetics of IFN-Gamma and TNF-Alpha Gene Expression and Their Relationship with Disease Progression after Infection withMycobacterium Tuberculosisin Guinea Pigs

“…Although the monkey model is currently an excellent animal model of human TB, this model has substantial limitations in terms of high cost of monkeys and the maintenance of facilities 16,17. Among these animal models, guinea pig is a relevant animal model of human TB since guinea pig is highly susceptible to M. tb and the spectrum of human TB can be biologically and pathologically displayed when infected with M. tb 18-24…”