Rodents as pre-clinical models for predicting vaccine performance in humans

Abstract

Vaccines represent a key building block for establishing a successful and sustainable control strategy against infectious diseases. Vaccine development often depends on the availability of correlates for protection and reliable animal models for the screening, selection and prioritization of potential vaccine candidates. This is performed according to their immunogenicity, efficacy and safety profiles in pre-clinical studies, which are also critical for identification of candidate antigens, selection of an optimal delivery system and design of appropriate vaccine formulations. Thus, pre-clinical studies in animal models are a prerequisite for addressing crucial issues and generating a solid pre-clinical package for the approval of clinical trials. This review addresses the strengths, limitations and perspectives of rodents as a vaccine development and pre-clinical validation tool.

Keywords:

• animal studies
• in vivo testing
• pre-clinical validation
• rodent models
• vaccine development

Acknowledgements

We are grateful to Blair Prochnow and Klaus Schughart for critical reading of the manuscript.

Financial & competing interests disclosure

This work was supported in part by grants from the EU (UniVax), BMBF in the context of the programs Gerontosys 2 (Gerontoshield), EuroNanoMed (HCVAX) and ERANetRUS (HCRUS), and the Helmholtz Association (HAI-IDR and cross-program activity "Metabolic Dysfunction and Human Disease”). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Due to the complexity of in vivo processes, alternative in vitro approaches such as cell culture or computer-based systems cannot fully replace animal pre-clinical validation studies.

• Regulatory guidelines require proof of concept and safety studies performed in relevant animal models prior to testing promising vaccine candidates in clinical trials.

• Small animal models represent a cost- and time-efficient strategy to perform the screening, selection and prioritization of vaccine candidates, as well as often the only logistic viable alternative to antigen selection programs (e.g., reverse vaccinology).

• The use of rodent animal models allows identifying potential vaccine candidates, evaluating the most efficient vaccine formulation and defining the optimal route of delivery.

• The development of improved rodent animal models (e.g., humanized mice) is expected to facilitate translation of pre-clinical observations into the human system.

• The increase of ethical concerns requires an in-depth and broad education of the public to emphasize the necessity of animal research in order to develop efficient vaccines.

• Animal studies should be supported by emerging in vitro and in silico approaches, and ruled by the three Rs principles.