Animal research

The Important Role of Animal Research in Developing a COVID-19 mRNA Vaccine – Speaking of Research

September 2, 2021

Speaking of Research commends the National Institute of Allergy and Infectious Diseases for issuing a statement of which our readers are keenly aware:

Basic and applied animal research has played a vital role in our response to the pandemic.

Statements like those of trusted experts are integral to the fact that those who oppose animal research continue to push forward false story that COVID-19 vaccines were not dependent on animal research (for example, here) and that animal research was not essential to ensure the safety and efficacy of these vaccines before they were administered to humans (p. here).

The important role of animal research in the development of an mRNA COVID-19 vaccine

As the global COVID-19 pandemic continues, safe and effective vaccines play a central role in preventing serious illness and death and limiting the spread of SARS-CoV-2, the virus that causes COVID -19. The emergency of the COVID-19 pandemic required rapid vaccine development and testing. Fortunately, NIAID’s decades-long support and conduct of coronavirus and vaccine research has laid the groundwork to help develop a safe and effective COVID-19 vaccine at record speed.

COVID-19 animal models

Animal research plays a key role in the development of effective vaccines for humans. Before promising vaccine candidates can be tested in humans, they must first be tested for safety and efficacy in animals, as required by the United States Food and Drug Administration. To do this, scientists first determine whether a candidate vaccine can stimulate an adequate and safe immune response. This important step is often achieved using small and then potentially larger animal models of disease. Mice are frequently used because they reproduce quickly, have a well-characterized immune system and a defined genome. Some labs have turned to models of mouse infection early in the COVID-19 pandemic to find that mice are not infected with SARS-CoV-2. To infect cells, SARS-CoV-2 must bind to a human protein called ACE2. Human and murine 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 therefore can be infected with SARS-CoV-2. When these genetically engineered mice get infected with the virus, they lose weight and get sick in a way similar to what happens when people get infected with the virus. Mouse models have provided vital information on COVID-19 symptoms and disease progression and continue to be used by researchers to understand COVID-19 disease.

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

The development of a vaccine against COVID-19 has also benefited from studies in non-human primates. By evaluating the immunogenicity and protection of vaccines in preclinical animal models, non-human primates offer several advantages for clinical translation. They are inbred, have greater similarity to humans than rodents in terms of innate immune responses and B and T cell repertoires, and allow the use of clinically relevant vaccine doses. Recent studies in non-human primates show that SARS-CoV-2 targets similar replication sites and recapitulates some aspects of COVID-19 disease. Non-human primates are used in the later stages of vaccine development and generally build on knowledge accumulated in previous small animal studies.

A new type of vaccine

The biopharmaceutical companies Moderna, Inc., based in Cambridge, Mass., And Pfizer, Inc., based in New York, have developed a new type of nucleic acid vaccine called an mRNA vaccine which, when used tested in clinical trials, found to be over 90 percent effective in preventing COVID-19. Animal studies have contributed to the scientific understanding of how these new types of mRNA vaccines work. For example, during the Zika virus outbreak in 2016, researchers developed a nucleic acid-based vaccine that protects against Zika virus infection in mice and non-human primates. Moderna and Pfizer COVID-19 vaccines use nucleic acid, messenger RNA (mRNA) to produce the viral spike protein found on the surface of SARS-CoV-2. Because mRNA is unstable, it is enclosed in lipid nanoparticles to prevent it from degrading after injection. The cells then produce the viral spike protein and display it on their surface. In this form, the viral spike protein is recognized by the body and triggers an immune response. This response includes the production of antiviral antibodies and T cell responses that allow the body to remember how to fight SARS-CoV-2 if infected in the future.

Preclinical data with Moderna’s mRNA vaccine has produced promising results in animal models. Experiments in mice have shown that a low dose of the vaccine induces a strong neutralizing antibody response and high level protection against SARS-CoV-2. In addition, vaccination of non-human primates with the mRNA vaccine induced robust neutralizing activity of SARS-CoV-2 and notably rapid protection of the upper and lower respiratory tract, similar to the safety and immunogenicity results observed by continued in a phase I human clinical study.

Male rhesus macaque. Source: Kathy West.

To look forward

Biomedical studies involving animal models have greatly contributed to the public health response to SARS-CoV-2 by aiding the development of COVID-19 vaccines and treatments. Animal studies will continue to provide vital information as new variants of SARS-CoV-2 emerge and new questions arise about the transmissibility of these variants, whether they are more harmful to humans and whether they remain. sensitive to available vaccines. Animal models play a critical role in pandemic response efforts as they are needed to assess the safety and effectiveness of new vaccines and treatments. Scientists will continue to use lessons learned from COVID to develop animal models as part of our pandemic preparedness efforts to target other emerging or re-emerging infectious diseases.

~ Speaking of research

* Extract from Press release of NIAID and edited for style and content.