Available COVID-19 vaccines are not as effective for immunocompromised people like cancer patients, but researchers are hoping to change that. Key TakeawaysCoVac-1, a new vaccine developed in Germany, was found to induce strong immune responses in immunocompromised people like cancer patients.The new vaccine enhances a response from T-cells, another type of immune cell that can help
A new COVID vaccine, called CoVac-1, produced a strong immune response in immunocompromised patients with cancers like leukemia and lymphoma. A team of German researchers from the University Hospital Tübingen developed the vaccine.
The results from the trial were presented at the American Association for Cancer Research Annual Meeting 2022 last week. CoVac-1 induced T-cell immune responses in 93% of patients with B-cell deficiencies.
B-cells and T-cells are white blood cells that help to protect against infection. B-cells make antibodies that attack bacteria and viruses, while T-cells attack cells that have been infected.
“To our knowledge, CoVac-1 is currently the only peptide-based vaccine candidate specifically developed and evaluated for immunocompromised patients,” Juliane Walz, MD, lead author of the study, and a professor at the University Hospital Tübingen, said in a statement.
Walz and her colleagues previously tested the safety and efficacy of the new vaccine in people without immune deficiencies and discovered those who received the vaccine maintained strong T-cell responses three months after vaccination. Based on these results, the researchers decided to test the vaccine’s efficacy in immunocompromised patients by carrying out a phase 1/2 clinical trial.
In phase 1 of the trial, the researchers analyzed 14 patients with B-cell deficiency, including 12 patients with leukemia or lymphoma. They were given a single dose of CoVac-1 and were observed for up to six months. The researchers said around 64% of patients in the study were previously vaccinated with an approved COVID-19 vaccine, but they failed to produce antibodies.
However, the study found that 14 days after the CoVac-1 vaccination, 71% of patients developed T-cell immune responses, which rose to 93% of patients 28 days after vaccination. The new vaccines produced T-cell responses that were better than what was observed in B-cell deficient patients who received an mRNA vaccine.
CoVac-1 is a peptide-based vaccine, which means it uses synthetic pieces of COVID-19 proteins sampled from different parts of the virus, William Werbel, MD, assistant professor of medicine and infectious disease expert at Johns Hopkins Medicine, told Verywell in an email.
In other words, these peptide-based vaccines are artificially made to mimic natural sequences.
This is combined with another substance (also known as adjuvant) that promotes a generally stronger immune response to the peptides. Since peptides are sensitive and poorly immunogenic, they need to be combined with an additional immune-stimulating agent.
J. Wes Ulm, MD, PhD, clinician, medical researcher, and bioinformatics expert at Harvard Medical School Hospital System, told Verywell in an email that Pfizer and Moderna shots use fatty bubble-like containers, called lipid nanoparticles (LNPs), to deliver messenger RNA (mRNA) directly to our cells.
The mRNA serves as a direct template to produce a sample of the viral spike protein which stimulates the human immune system against the virus.
Current COVID-19 vaccines target the virus’s spike protein, which the virus uses to enter and infect human cells. However, the immune system recognizes the spike protein does not belong there and triggers the production of antibodies to fight off the infection.
However, the CoVac-1 vaccine provides only snippets of viral proteins (called antigens) in an injectable package that is then delivered into the body. These antigens are unique peptide sequences that are specific to several proteins of COVID-19.
“The resulting immunostimulation then engenders a broad and potent immune response that is nonetheless specific for SARS-CoV-2, and is more robust in many respects to viral mutation in comparison to the more commonly administered vaccines,” Ulm said.
Although early results from a small clinical trial show a new COVID vaccine can induce a robust immune response in immunocompromised patients, larger clinical trials that include diverse populations are needed.
While current vaccines that are approved for use induce a robust immune response against COVID-19 in a majority of individuals, they aren’t necessarily effective in many immunocompromised people, including cancer patients, Walz and her colleagues stated.
“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination,” Walz said. “These patients are thus at a high risk for a severe course of COVID-19.”
Werbel added that for people with immunodeficiencies, the current vaccines “may produce blunted antibody and cellular responses. This factors into the higher rates of infections after vaccination like breakthrough infections.”
Current vaccines contain a piece of the virus that tricks the body into thinking it has been infected. This process then causes the body’s natural immune system including the B-cell response to activate. But for some immunocompromised patients who undergo chemotherapy and other immunotherapies, their B-cells get destroyed, a strong reason why current vaccines aren’t as effective for immunocompromised people.
Furthermore, Werbel said chemotherapies erode bone marrow and lymphoid tissue that eliminate cells like B-cells. Other targeted therapies and medications destroy or impair B-cells.
“Recipients of these therapies and medications frequently cannot generate impressive antibody responses to vaccines for several months,” Werbel said.
The authors of the study noted one way to compensate for this is to enhance the response from T-cells.
Ulm explained that B-cells tend to be depleted more thoroughly than T-cells, and so cancer patients often have a greater degree of residual T-cell function, which CoVac-1 is able to utilize in providing active immunity.
Even though there are other prevention options available for immunocompromised people like AstraZeneca’s Evusheld, the first monoclonal antibody treatment, Werbel said these products do not evoke cellular responses like B-cell memory or T-cell immune response to COVID-19.
“Medications like Evusheld are monoclonal antibody products which typically include potent combinations of a couple of anti-spike protein antibodies that can be infused or injected to provide so-called ‘passive’ immunization,” Werbel explained. “Importantly, they appear to be more susceptible to immune evasion by viral variants, because changes in the virus proteins evade these very targeted products (which are narrower than the repertoire of antibodies that a person’s immune system can generate). This is why medications like Evusheld are complements to vaccines, not substitutes.”
Richard Reithinger, PhD, vice president for Global Health at RTI International, told Verywell from a patient perspective, this new data is welcome news since it seems to indicate that people with B-cell deficiencies are responding better to the CoVac-1 vaccine than other vaccines that have been used to date.
But he emphasizes that more data is needed since the data presented is from a phase 1/2 clinical study and only included a sample size of 14 individuals.
“Larger clinical trials with a bigger sample size and a more diverse group of individuals will have to confirm those initial results,” he said. “From a public health perspective, even if these initial results were to be confirmed in larger clinical trials and the CoVac-1 would be recommended as a vaccine for immunocompromised people, the effect on SARS-CoV-2 transmission and the pandemic would be very limited since in the U.S. people who are moderately or severely immunocompromised represent about 3% of the population.”
The researchers are currently preparing for a phase 3 clinical trial in which they will evaluate the effectiveness of CoVac-1 in a larger population of immunocompromised individuals.
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