Washington National Primate Research Center

August 18, 2021

NIAID Now: The Important Role of Animal Research in mRNA COVID-19 Vaccine Development

As the global COVID-19 pandemic continues, safe and effective vaccines are playing a pivotal role in preventing severe disease and death and limiting the spread of SARS-CoV-2, the virus that causes COVID-19. The urgency of the COVID-19 pandemic necessitated rapid vaccine development and testing. Fortunately, NIAID’s decades-long support and conduct of coronavirus and vaccine research laid the groundwork for helping to develop a safe and effective COVID-19 vaccine in record speed.

COVID-19 Animal Models

Animal research plays a key role in developing successful vaccines for humans. Before promising vaccine candidates can be tested in humans, they must first be tested for safety and effectiveness in animals as required by the U.S. Food and Drug Administration. To do this, scientists first determine whether a vaccine candidate can stimulate an adequate and safe immune response. This important step is often conducted using small and then, potentially, larger animal models of disease. Mice are frequently used because they reproduce rapidly, have a well-characterized immune system and a defined genome. Some labs turned to mouse models of infection early in the COVID-19 pandemic only to find that mice don’t get infected with SARS-CoV-2. In order to infect cells, SARS-CoV-2 must bind to a human protein called ACE2. The human and mouse ACE2 proteins are different, and SARS-CoV-2 does not bind to mouse cells. Scientists overcame this problem by generating mice that can express the human version of ACE2 and can therefore be infected with SARS-CoV-2. When these genetically modified mice are infected by the virus, they lose weight and become sick in ways that are similar to what happens when people are infected with the virus. Mouse models provided vital information about COVID-19 symptoms and its disease course and continues to be used by researchers to understand COVID-19 disease.

Syrian hamsters are another important animal model for COVID-19 because disease in those animals closely resembles the disease in humans. Additionally, older male hamsters develop more severe disease than young female hamsters, which reflects some of the differences seen in humans infected by SARS-CoV-2. Hamster models have contributed to the evaluation of investigational COVID-19 vaccine candidates, immunotherapies, and antiviral drugs.

Vaccine development for COVID-19 also benefitted from nonhuman primate studies. In assessing immunogenicity and protection of vaccines in pre-clinical animal models, nonhuman primates provide several advantages for clinical translation. They are outbred, have greater similarity to humans than rodents in innate immune responses and B- and T-cell repertoires, and allow use of clinically-relevant vaccine doses. Recent studies in nonhuman primates show that SARS-CoV-2 targets similar replication sites and recapitulates some aspects of COVID-19 disease.  Nonhuman primates are used during the later stages of vaccine development and typically build upon the knowledge accumulated in earlier small animal studies.

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