Sathkumara, Harindra D., Valencia-Hernandez, Ana Maria, and Kupz, Andreas (2025) Pre-clinical studies and animal models. In: Bettencourt, Paulo J.G., (ed.) Tuberculosis Vaccines. Springer, pp. 153-202.

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Abstract

To assess their safety, immunogenicity, and efficacy all vaccine candidates must undergo pre-clinical evaluation before clinical trials can be considered. In the case of TB, most experimental vaccines are compared to BCG and sometimes to other parental vaccine constructs during pre-clinical development. To understand immunogenicity, on which successful vaccination ultimately depends, in vitro studies can be used to examine vaccine constructs on isolated immune cells, cell co-cultures, and organoids. However, a disadvantage arising from the use of these systems is the detachment of the cells from their normal physiological environment. The lack of interaction with other cells and the growth in an artificial medium does not fully correspond to the physiological in vivo conditions. Although experimental results obtained in this way can give a first indication of specific immune mechanisms, the precise mode of action in the whole body cannot be predicted accurately. The immune response is a very complex, spatially, and temporally precisely regulated process in which even small changes in certain parameters can lead to significant changes in the overall system. To date, the complexity of the mammalian immune system cannot be recapitulated by any in vitro method, and the safety and efficacy of a vaccine can only be evaluated by conducting vaccination-challenge experiments in live animals. In this chapter, we first describe how some in vitro methods can be used for the initial screening of experimental TB vaccines. We then discuss the advantages and disadvantages of various vertebrate animal models that have been used to study the safety, immunogenicity, and efficacy of TB vaccines. Finally, we finish the chapter with some insights into the impact of different vaccination routes and the Mtb challenge dose.

Item ID:	87008
Item Type:	Book Chapter (Research - B1)
ISBN:	978-3-031-94540-3
Copyright Information:	© 2025 The Author(s), under exclusive license to Springer Nature Switzerland AG
Date Deposited:	02 Sep 2025 23:54
FoR Codes:	31 BIOLOGICAL SCIENCES > 3107 Microbiology > 310702 Infectious agents @ 50% 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320701 Medical bacteriology @ 50%
SEO Codes:	28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280103 Expanding knowledge in the biomedical and clinical sciences @ 100%
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