Not Just About Antibodies: Why mRNA COVID Vaccines May Shield From Variants

TUESDAY, May 4, 2021 (HealthDay News) -- Two widely used COVID-19 vaccines — Pfizer and Moderna — will likely remain powerfully protective against developing serious illness even if coronavirus variants somehow manage to infect vaccinated patients, new research suggests.

Both vaccines are based on messenger RNA (mRNA) technology. And investigators say that, at least in theory, such technology can deploy multiple levels of defense to keep ever-changing coronavirus variants in check.

"It is important to note that only time will tell whether the vaccines do in fact protect against other human coronaviruses," cautioned study author Dr. Joel Blankson, a professor of medicine at Johns Hopkins Medicine, in Baltimore. "But this could be a good news story."

The reasoning, said Blankson, is that both the Pfizer and Moderna vaccines actually do two things at once.

On the one hand, the vaccines trigger the immune system into producing protective antibodies. "In terms of COVID-19, antibodies would work to prevent virus from infecting cells" in the first place, he explained.

At the same time, the vaccines also cause the immune system to generate so-called "helper T-cells," known as CD4+ T lymphocytes. "And T-cells would kill cells that are infected, to help prevent the infection from spreading," Blankson said.

CD4+ T-cells do this by setting in motion a chain of immune-bolstering events, including the activation of a particularly powerful "killer" T-cell known as CD8+, the study team noted.

After conducting an in-depth blood sample analysis, Blankson's team found that such killer T-cells seem to keep the coronavirus firmly in the immune system's crosshairs, even if antibodies designed to combat an early iteration of the virus fail to prevent infection with a newer variant.

The blood analysis involved 30 men and women, ranging in age from 20 to 59. All had been vaccinated with two doses of one of the two mRNA vaccines, and none had tested positive for COVID-19 either prior to vaccination or afterwards. Both the Pfizer and the Moderna vaccine are approved for emergency use in the United States. Another approved vaccine produced by Johnson & Johnson is based on a different technology, and was not included in the study.

As intended, the mRNA vaccines first triggered the production of a harmless version of a "spike protein" found on the surface of the coronavirus. That, in turn, launched each recipient's immune system into action, generating antibodies to fight off infection.

But beyond that, initial lab tests revealed that the mRNA vaccine also produced a strong T-cell response following exposure to the original strain of the coronavirus.

That initial response generated 23 different types of T-cell protein building blocks (or peptides). And subsequent blood analyses further showed that fewer than one-fifth of those peptides seemed to be impeded by newer coronavirus strains, such as the ones that recently took hold in the United Kingdom and South Africa.

According to Blankson, "T-cells and antibodies recognize different parts of the spike protein, and the parts of the variant proteins that allowed them to partially evade the antibody response are not important for T-cell recognition."

And that, he added, means that "even if the variants are able to escape the antibody response and infect cells, T-cells should be able to kill infected cells before the virus replicates to a high level that would cause severe disease."

A number of researchers offered upbeat reactions to the findings.

"Yes, it is a good story," said Rustom Antia, a professor in the department of biology at Emory University and affiliate faculty with Emory Vaccine Center, in Atlanta.

"The implications are that having a coordinated immune response with multiple components is better than one that is focused on a single component. Much like waging a successful military campaign requires Army, Navy and Air Force," said Antia.

Suzanne Judd, an epidemiologist and professor in the school of public health at the University of Alabama at Birmingham, agreed. "From a disease control and prevention standpoint, these research findings are as good as it gets," she said.

Blankson and colleagues "demonstrate that the vaccine can stop the spread of variants, which if true means we can be more comfortable returning to normal," Judd added.

At the same time, both Blankson and Judd said that other non-mRNA vaccines might end up proving equally adept at staving off serious illness.

"We don't have enough information to know if the J&J and AstraZeneca vaccines produce the same type of T-cell response yet," Judd noted. "The results of this study don't mean the same response is not true for other types of vaccines, because they did not examine other types of vaccines."

Indeed, Dr. David Hirschwerk, an attending infectious disease and internal medicine physician with Northwell Health in Manhasset, N.Y., said that "while this study looked only at mRNA vaccines, it does seem likely that the T-cell responses will be similar" in other vaccines like J&J, though he stressed that more research will be needed to know for sure.

He agreed that the latest finding "does add a layer of reasoning to why the vaccines appear protective against most of the important variants currently circulating." But, Hirschwerk stressed that "we still primarily need to rely upon the clinical observations of how patients infected with variants continue to fare over time after vaccination."

The report by Blankson's team was published recently in the Journal of Clinical Investigation.

More information

There's more on how mRNA vaccines work at the U.S. Centers for Disease Control and Prevention.

SOURCES: Joel N. Blankson, MD, PhD, professor of medicine, department of medicine, Johns Hopkins Medicine, Baltimore; Rustom Antia, PhD, professor, department of biology, Emory University and affiliate faculty, Emory Vaccine Center, Atlanta; David Alan Hirschwerk, MD, attending physician, infectious disease and internal medicine, Northwell Health, Manhasset, N.Y.; Suzanne Judd, PhD, epidemiologist and professor, School of Public Health, University of Alabama at Birmingham; Journal of Clinical Investigation, April 6, 2021, online