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Dr Govinda Sharma By Dr Govinda Sharma • July 9, 2020

COVID-19 FAQ: how cracking the secrets of T Cells can give vaccine design a boost?

When we hear about SARS-CoV-2 immunity we mostly think: antibodies. These proteins are made by a group of immune cells, called B cells. Antibodies find and bind to foreign proteins in our bodies. They lock onto their targets, they signal other immune cells to come and clean up the infection. But less is known of the key role of T cells – the cousins of B cells – in immunity.

Understanding T cell reactions can help improve vaccine design for COVID-19

T cells are the backbone of the immune system. They use specialised receptors (TCRs) to inspect cell surfaces. If they find their proteins of foreign origin (for example, originating from viruses), the T cells either kill the infected cell or start recruiting and boosting other immune cells in the area. It is  T cells that prompt B cells to start making antibodies, but what triggers them? What we know is that they can react to many protein fragments (called epitopes) even to ones that belong to the SARS-CoV-2 virus. A recent study out of La Jolla Institute for Immunology in California demonstrated that such T cell responses were detectable in 40-60% of people who were never exposed to the virus and in 70-100% of people who recovered from mild COVID-19. These results dispel fears that we cannot develop immunity to COVID-19 or will get re-infected.
 
So what do T cells target on the coronavirus? We’ve also learned from the La Jolla study, that T cell responses are directed against several SARS-CoV-2 proteins, not just the notorious ‘spike protein’, which has been the central focus of vaccine research so far. This finding is encouraging because it means a multitude of options has opened up to vaccine designers for using different targets on the novel coronavirus to induce immunity. We still need to learn, however, which specific epitopes (or minimal fragments of these viral proteins) can trigger responses from T cells. Figuring this out would be a big boost: it would let us develop peptide vaccines (peptides are another name for small protein fragments of the type that make up T cell epitopes). These have someadvantages over whole protein or live attenuated virus-based vaccines as they lower the risk of allergic and autoimmune reactions. They could also lead to soluble TCR-based therapeutics (

where TCRs are engineered to float through tissues without being bound to a cell, like antibodies do. The advantage here is  that they are still able to recognise the whole spectrum of epitopes that T cells can see but which antibodies cannot do.) This technology is already being explored in cancer therapy. 

Discovering the specific epitopes that T cells react to is easier said than done because of the complex nature of TCR/epitope interactions. Research groups are using computers to predict possible epitopes that might make for good SARS-CoV-2 vaccine candidates. These strategies are not so accurate at the moment and real-world lab testing is still essential. Fortunately, a slew of techniques, including a platform we’ve previously published on and patented, has been developed to search through sets of possible epitopes and find ones that can provoke immune responses. We’ve been applying our discovery technology towards finding T cell responses to SARS-CoV-2 in unexposed and recovered individuals and building on the La Jolla study by attempting to recover relevant epitopes in the process.
 

Here is the current state of science on a Sparrho pinboard. NB: The pinboard contains research papers that have not been peer-reviewed yet, meaning that they have not gone through the standard scientific validation process yet.

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