30/07/2020

T-Cell Response Central to Coronavirus Vaccine Hopes

Encouraging new research suggests rapidly decreasing antibody levels don’t necessarily limit the effectiveness of potential vaccines

While the media have been awash with doomsday reports that an effective COVID-19 vaccine is hopeless due to the seemingly despairing rate at which people’s immune response to the virus dissipates over time, two recent peer-reviewed papers provide increasingly strong support for the notion that an effective vaccine is, indeed, possible.

The two papers focus on T-cells (which play a central role in the body’s immune response system), comparing their presence in people infected with either SARS-CoV 2 (the virus which causes COVID-19) or SARS-CoV (the so-called “original SARS” from 2003, and the most closely related human coronavirus to the current strain) against a control group of people who haven’t been exposed to either of the viruses.

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The first paper, titled “Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals” and published in May 2020 in Cell, demonstrated two important findings. First, it showed that the T-cell response to the latest coronavirus is less extreme than its response to SARS-CoV (the 2003 SARS). Second, it showed that some people who haven’t been exposed to either SARS-CoV or SARS-CoV 2 nevertheless have T-cells that recognize the new virus. The important implication here, as speculated by the authors, is that there could be a portion of the population which already have some protection against the latest coronavirus, even if they don’t have antibodies for the virus (they haven’t been infected). If so, the effort to contain the pandemic by reaching so-called herd immunity through vaccination, would be supported.

The second paper, “SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls,” published in July in Nature, confirmed the first paper’s findings. It showed that T-cell responses to SARS-CoV-2 reacted on the same proteins as those identified in the first paper, thereby replicating the first paper’s results in that regard. Secondly, the latter paper, like the first, also showed that people who haven’t been exposed to either SARS-CoV or SARS-CoV-2 nevertheless still have T-cells that react to protein antigens from the latest virus. This, again, supports the conjecture that there could be a portion of the population who already have some protection against the latest coronavirus.

The latter paper goes a step further, showing that T-cell response is long lasting and that it acts on similar proteins across coronavirus strains. The authors did this by first demonstrating that patients who recovered from SARS 2003 still have a robust T-cell response (17 years later!) to SARS 2003’s N protein. Critically, the authors also demonstrate that the T-cell response cross-reacts with the N protein associated with COVID-19. This is important as it could explain why, despite the rapid drop in antibody responses shown by people who are recovering from COVID-19, there are practically zero credible cases of people actually being re-infected with COVID-19. Again, the implication is that a vaccine which targets the appropriate T-cell reaction would, in fact, have lasting effect.

Moving forward, as it relates to the development of effective vaccines, it’s important for researchers to determine both the proportion of the population that have coronavirus-reactive T-cells despite having not been exposed to either SARS-CoV 1 or 2, as well as the level of protection that those T-cells offer. Secondly, we need to know how long T-cell reactivity lasts for SARS-Cov-2, as that will determine how often we need to re-vaccinate. Finally, and this is the critical piece when it comes to vaccine development, we need to determine exactly which T-cell responses are induced by vaccine candidates.

About the Author:

ClinTex are a solution provider to the pharmaceutical industry, and the team behind CTi — Clinical Trials Intelligence: a new type of software platform aimed at transforming the medicine development industry through the application of predictive analytics, machine learning, and the novel use of blockchain technology and smart contracts in clinical trials.

Our mission is to bring down the cost of medicine and improve the speed to market of new medicines for the people who need them, through vastly reducing development costs for the global pharmaceutical industry.

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