Animal Models to Test SARS-CoV-2 Vaccines: Which Ones Are in Use and Future Expectations

Abstract

Since late 2019 and early 2020, with the emergence of the COVID-19 pandemic, scientists are rushing to develop treatment and prevention methods to combat SARS-CoV-2. Among these are vaccines. In view of this, the use of animals as experimental models, both to investigate the immunopathology of the disease and to evaluate the efficacy and safety of vaccines, is mandatory. This work aims to describe, through recent scientific articles found in reliable databases, the animal models used for the in vivo testing of COVID-19 vaccines, demonstrating some possibilities of more advantageous/gold-standard models for SARS-CoV-2 vaccines. The majority of the studies use rodents and primates. Meanwhile, the most adequate model to be used as the gold standard for in vivo tests of COVID-19 vaccines is not yet conclusive. Promising options are being discussed as new tests are being carried out and new SARS-CoV-2 variants are emerging.

Keywords: SARS-CoV-2; animal model; coronavirus; gold standard; new variants; vaccine.

Figure 1

Representation of vaccine development stages. First, exploratory research is conducted to better understand the pathogen. The most conserved and possibly immunogenic antigens are investigated and isolated. New technologies, such as gene sequencing and bioinformatics tools, are applied. In the SARS-CoV-2 case, the main antigens that have been used in vaccine development are the spike, the receptor-binding domain (RBD), and nucleocapsid proteins. The pre-clinical phase involves animal studies. It usually starts in smaller models, such as rodents, then moves onto translational models, such as non-human primates (NHP). The following phases (I, II, III, and IV) focus on human studies. The number of volunteers increases along with the phases. Safety, immunogenicity, and overall effectiveness are analyzed. When thousands of people are being vaccinated, the monitoring continues to verify rare adverse effects.