Ex vivo challenge models for infectious diseases

Abstract

Traditionally, molecular mechanisms of pathogenesis for infectious agents were studied in cell culture or animal models but have limitations on the extent to which the resulting data reflect natural infection in humans. The COVID-19 pandemic has highlighted the urgent need to rapidly develop laboratory models that enable the study of host-pathogen interactions, particularly the relative efficacy of preventive measures. Recently, human and animal ex vivo tissue challenge models have emerged as a promising avenue to study immune responses, screen potential therapies and triage vaccine candidates. This approach offers the opportunity to closely approximate human disease from the perspective of pathology and immune response. It has advantages compared to animal models which are expensive, lengthy and often require containment facilities. Herein, we summarize some recent advances in the development of ex vivo tissue challenge models for COVID-19, HIV-1 and other pathogens. We focus on the contribution of these models to enhancing knowledge of host-pathogen interactions, immune modulation, and their value in testing therapeutic agents. We further highlight the advantages and limitations of using ex vivo challenge models and briefly summarize how the use of organoids provides a useful advancement over current approaches. Collectively, these developments have enormous potential for the study of infectious diseases.

Keywords:

• Ex vivo challenge
• tissue explant
• organoids
• pathogens
• mucosa

Authors’ contributions

BGG, DL and BDK conceived the structure of the review and jointly drafted the manuscript; GS, CH, FC, NM and JF contributed to editing the review. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the South African Medical Research Council, the National Research Foundation, the Department of Science and Innovation; and the European and Developing Countries Clinical Trials Partnership (EDCTP) [grant number RIA2020EF-3008].