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As Covid-19 sweeps across the globe, and the number of cases in South Africa grows on a daily basis, we are eagerly awaiting the arrival of an effective vaccine.
Health24 recently published an article explaining why clinical trials are key to ensure the safety of any medication, and why it may still be a while before we have a Covid-19 vaccine.
Researchers at Baylor College of Medicine and Texas Children’s Hospitals are experiencing first hand the challenges surrounding the development of a new vaccine.
Vaccines, pathogens and the immune system
The National School of Tropical Medicine at Baylor and the Center for Vaccine Development at Texas Children’s Hospital are currently in the process of developing a coronavirus vaccine.
The key goal of a vaccine is to trigger an immune response that will fight off a virus, but still be safe enough not to make the person sick. This is true for all vaccines, but the end product is different for each pathogen.
According to Dr Maria Elena Bottazzi, vaccine development is a balancing act between design and the immune response.
"As we proceed with the designing and testing of vaccine candidates, we felt the need to collaborate with a clinical immunologist, who also is engaged in basic and translational research, so that together we can inform our vaccine development efforts and ensure we evaluate both the protective mechanisms and avoid inducing any undesirable immunological responses that have been associated with some respiratory viruses," she stated in a news report.
Bottazzi and fellow researcher Dr Peter Hotex approached Baylor’s pulmonologist Dr David Corry – professor of immunology, allergy and rheumatology and Fulbright Endowed Chair in Pathology in the Department of Pathology and Immunology – to collaborate.
Their research outcomes are published in the journal Nature Reviews Immunology, where an analysis of the vaccine development strategy can be read.
How does a vaccine protect against Covid-19?
While there is still a lot to be researched about SARS-CoV-2, the virus responsible for Covid-19, researchers now know that our bodies are most likely protected from the virus by a robust antibody response with a neutralising capacity.
We also need an immune response where the release of cytokines is balanced, as to not cause illness.
Previous studies have shown that it might be possible to develop protective antibodies.
"We are encouraged by the evidence supporting the likelihood that immunising against the spike protein's receptor-binding domain represents a realistic and viable vaccination strategy. However, many questions remain," said Dr Hotez in a statement.
"Studying the immunological responses triggered in people infected by the virus is one way researchers can select what viral components or antigens are promising candidates to use when designing the vaccine," Bottazzi said. "That, coupled with studies using laboratory models of disease, is how scientists attempt to predict what are the ideal mechanisms of protection triggered by vaccines," he remarked.
What could go wrong?
As a vaccine’s main goal is to trigger an immune response without harming the body, the researchers have looked at the effects of their previous developments in two ways – how a vaccine influences the immune system and what it does to the cells.
According to the news release, experimental and pre-clinical observations in earlier vaccine attempts against respiratory viruses showed that some of the formulations may trigger negative responses by the immune system.
Pre-clinical testing also showed that there could be tissue damage caused by cellular infiltrates after an immune response.
"Some experimental animals developed an inflammatory response in the lung or liver characterised by significant infiltration of immune cells – lymphocytes, monocytes and eosinophils," Corry said. "Our literature search suggests that this cellular infiltration can be associated with IL-6, a cytokine or immune protein that is strongly increased in patients with Covid-19 who experience a cytokine storm, an excessive production of cytokines that can be life-threatening."
There might also be undesirable responses from antibodies. While this has happened with other viruses, Bottazzi and team haven't observed it in their vaccines: "We have not found any evidence that our vaccine triggers antibody-dependent enhancement in laboratory pre-clinical experiments. Experimental evidence suggests that our vaccine against the receptor-binding domain leads to the neutralisation of the virus," Bottazzi said.
"Pre-clinical studies, performed with our partners at the University of Texas Medical Branch, show that the receptor binding domain on alum is indeed a promising vaccine candidate. It can trigger an immune response that is protective and does not induce undesirable cellular immune responses. We are working to advance this approach into the clinic for phase 1 studies," Bottazzi added.
Time needed to find the right vaccine
While vaccine development has always been challenging, scientists are collaborating like never before, according to the research team.
"We believe that we need to have many vaccine candidates, platforms and trials, so we can evaluate as many vaccine options as possible to select the ones that are the most appropriate and prove to be the most effective and safe," said Hotez.
"We invested almost a decade of research to maximise immune protection and minimise or prevent immune enhancement. Ultimately our goal is that these vaccines are made for the global population, accessible and affordable to all."
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