How scientists are looking at T cells to develop stronger vaccines
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The mRNA coronavirus vaccines are effective in lowering risk of severe disease and death.
Some people, like many who are immunocompromised, may not have as strong of an immune response to those vaccines.
A peptide vaccine candidate being developed in Germany is meant to induce a response in T cells, which can then attack infected cells directly.
Researchers in Germany are taking a novel approach to strengthening coronavirus protections for immunocompromised people by developing a vaccine that targets T cells — which are important for long term immune response. It’s similar to an approach scientists are using to fight Alzheimer’s, which has seen progress in recent years. The hope is that the research could lead to a new vaccine that might save the lives of cancer patients, the elderly and others in need.
A team at the University Tübingen and University Hospital Tübingen are in the process of testing a vaccine that includes six peptides, which are short compounds made from the same building blocks as proteins that attach to and activate the body’s T cells, which are a type of white blood cell. These peptides usually show up on the outside of infected cells, which is how T cells can naturally find and bind to them. The cells can go on to kill infected cells that they recognize.
Other research groups have explored the possibility of using vaccines to target T cells that can bind to amyloid-β peptide, which has a role in the development of Alzheimer’s disease, and the plaques it forms in the brain. Some of these potential vaccines have been tested in animal models. One of the challenges in this area of research is that sometimes patients experience a T cell-mediated autoimmune response which could lead to unwanted inflammation.
For this SARS-CoV-2 vaccine, the researchers at the University Tübingen analyzed a large cohort of samples and used a multi-step computational analysis to determine which peptides to include and conducted tests to see how well they would induce T cell responses.
A preliminary trial included healthy adults with no known immune system issues, and all of these participants had a T cell response to the vaccine. In the phase I/II clinical trials, the team further tested the safety and immunogenicity of the vaccine, named CoVac-1. The participants included cancer patients, people who are immunocompromised and people who have deficiencies in B cells, the immune cells that produce antibodies, and may have trouble producing antibodies in response to mRNA and other types of vaccines.
Overall, 93 percent of the participants had a T cell response by day 28. “No inflammatory adverse events like fever occurred,” says Claudia Tandler at the Department of Peptide Based Immunotherapy of the University Tübingen and who presented the research at the American Association for Cancer Research Annual Meeting. This suggests this is a “really well tolerated vaccine administration,” she continues.
This peptide vaccine is not meant to replace the already authorized mRNA vaccines, which target B cells to produce antibodies. “This would be one approach, using peptide-based vaccines to specifically target T cells,” says Tandler. “Because not only the B cells are important for the immune defense, but also the T cells, especially in viral infections.”
The immunocompromised patients in the trial had previously received mRNA vaccine doses and the researchers found that their response to CoVac-1 was stronger. However, the final results of the phase II part are still to be determined. “Right now the follow-up analyses are ongoing and we presented the latest data at the conference,” says Tandler. They have data until day 28 and are currently collecting samples at later time points up to six months as part of the phase II clinical trials.
Although these results are promising, there is a long road ahead if this vaccine is to get into the bodies of more people. After the phase II trial, the next phase is a large-scale phase III trial. The current trial includes 40 participants, whereas a phase III trial would require thousands of participants. It would then take time to get the vaccine produced to finally be available to the general population.
Other than cancer patients and populations with B cell deficiencies, this vaccine could be another tool to help older adults whose immune systems may not be able to work up as strong of a response to mRNA vaccines. Tandler tells Changing America, this vaccine could be used as an additive vaccine to further boost or strengthen the immune response in the elderly people who tend to have a weaker humoral immune response to the currently approved vaccines against SARS-CoV-2.
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