T-Cells: The Powerful Promise of Long-Term COVID-19 Immunity?

“The T-cells response to SARS-CoV-2 infection has been largely ignored for the past year.”

Vincent Racaniello, Professor  of Microbiology and Immunology at Columbia University

Data is now emerging from several studies that the Pfizer COVID-19 vaccine induces less of a robust antibody response than its competitor, Moderna. A recent article from Market Watch states, “A study comparing individual immune responses to two major COVID-19 vaccines has shown that Moderna’s created more than double the antibodies than that of Pfizer and BioNTech.” However, the publication Stat reports that participants from the Pfizer Phase 3 efficacy study of the Covid vaccine show vaccinated participants “have protections against the virus by day 12, at a time when there’s barely any antibody response. 

Taken together, these two data sets seem to contradict one another.  After all, if the Pfizer vaccine is not prodiucing the same antiboyd respones as Moderna,it should not be as effecitve.

Yet, it’s just not true. Current data shows that the Pfizer vaccination has a 95% efficacy rate at preventing symptomatic COVID-19 illness and nearly 100% at preventing hospitalization due to COVID-19 complications, much like Modera, even though research shows Moderna produces nearly double the antibody response, which is traditionally considered to be an indicator of a more efficacious vaccine. As Vidia Roopchand, principal scientist for viral vaccines at Pfizer states, “The 12-day protection data is telling us there’s more to it.”

So, what gives?

Although it’s too early to draw any hard conclusions, scientists think it has something to do with the other immunological response elicited by the Pfizer vaccine: T-cells and B-cells. Although both antibodies as well as T-cells and B-cells are immunological responses that attack and kill viruses, T-cells and B-cells have a more specialized function than their antibody counterparts. 

According to Arizona State Univeristy’s School of Life Sciences (ASUSLS), “T-cells are a type of white blood cell that work with macrophages. Unlike macrophages that can attack any invading cell or virus, each T-cell can fight only one type of virus. You might think this means macrophages are stronger than T-cells, but they aren’t. Instead, T-cells are like a special forces unit that fights only one kind of virus that might be attacking your body.”

B-cells also attack invading orgainisms, but function a bit differently. As ASUSLS explains, “B-cells can connect to antigens right on the surface of the invading virus or bacteria. This is different from T-cells, which can only connect to virus antigens on the outside of infected cells.” 

Another distinguishing characteristic is their reponses over time. When you get a virus vaccine, your body produces antibodies in response. Thus far, the primary focus by COVID-19 vaccine creators has typically been on Immunoglobulin M (IgM) and Immunoglobulin G (IgG).

While IgM is the first antibody response that kicks in when our immune system is confronted with a virus or other disease-causing pathogens, it accounts for roughly 10% of all antibodies that the body produces, according to Dennis Sifris, MD. On the other hand, Sifris writes, IgG “takes longer to produce than IgM, but is the predominant antibody found in blood and other body fluids.” These antibodies work together to eradicate invading microorganisms, such as SARS‑CoV‑2.

However, recent data indicate that this antibody component of vaccination wanes over time. This is where T-cells may pick up the slack, because unlike the isolated antibody focus currently guiding vaccine research and  production, T- and B-cells may offer a more comprehensive approach that combat infection in the long run, after immunoglobulin antibodies have begun to lose their effectiveness.

This is because of a unique attribute of these specialized cells which allows them to retain a sort of “genetic memory” of the invading virus. This genetic memory can then be put into play should people get infected, thus providing immunological protection from severe symptomology for years down the road. 

Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

This notion is supported by research. In the article T Cell Memory: Understanding COVID-19, the researchers concluded, “Since effective immune memory can persist for decades and typically results in enhanced responses and accelerated pathogen control, generation of robust and durable T and B cell memory is a goal of vaccines, including the many vaccines against SARS-CoV-2 that are currently in human trials.”

In reality, scientists are already expressing concern about how the efficacy of a COVID-19 vaccine is measured, which is solely an immunoglobulin response. Marc Hellerstein, campus professor in the department of nutritional sciences and toxicology at UC Berkely, argues “Antibodies really are not enough. In fact, there’s a lot of data that says the more antibodies you have, the sicker you get. We need a different perspective and use different criteria for evaluating when a vaccine should be approved.” 

After reviewing previous literature on coronaviruses, including severe acute respiratory syndrome and the Middle East respiratory syndrome, Hellerstein concludes, “For most viruses, antibodies are great, but for coronaviruses, there’s a lot of evidence that antibodies are not sensitive for mild infections,” adding “They last, at most, a couple [of] years, sometimes even a few months, and they may even cause damage.” 

This perspective is echoed by Vincent Racaniello, a Higgins Professor in the Department of Microbiology and Immunology at Columbia University’s College of Physicians and Surgeons.  Racaniello points out, “The T cell response to SARS-CoV-2 infection has been largely ignored for the past year. Certainly, some laboratories have studied T cell responses in patients, and the vaccine makers have dutifully included them along with assays for neutralizing antibodies. But the dialogue has never included T cells as important for resolving disease – but they are for most viral infections. Because T cells can kill virus-infected cells, they can help prevent disease and end the infection.” 

To bolster his argument, Racaniello references a study that concluded that T-cells were able to recognize multiple SARS-CoV-2 strains, meaning they would theoretically target and destroy a variety of mutations down the road. And Racaniello is not alone in emphasizing the need to focus on T-cell response. In the research review, SARS-CoV-2 variants, spike mutations and immune escape, the authors make the following argument: “A comprehensive understanding of the consequences of spike mutations for antigenicity will encompass both T cell-mediated immunity and non-spike epitopes recognized by antibodies.”

Across the pond in the U.K., researcher Sarah C. Gilbert of the Jenner Institute at the  University of Oxford, shares these concerns, arguing, “Although some highly effective antibody-inducing vaccines against viral and bacterial diseases are available, to protect against more complex pathogens it will be necessary to engage the other arm of the adaptive immune system: T cells.”

And Dr. Dan Barouch of Beth Israel Deaconess Medical Center, who studied the efficacy of T-cells in monkeys, agrees with the importance of the role of T-cells, saying, “Antibodies alone can protect, including at relatively low levels, but T cells are also helpful if antibody levels are insufficient,” Barouch says. “Such knowledge will be important in the development of next-generation vaccines, antibody-based therapeutics, and public health strategies for COVID-19.”

Moreover, a recent study by Perelman School of Medicine at the University of Pennsylvania reveals that the Pfizer and Moderna vaccines, which both utilize an mRNA technology, have the same effect on generating T-cell responses as people who actually contract COVID-19, thereby potentially conferring long-term protection against future SARS‑CoV‑2 infections.

“Our findings underscore the fact that we need to look at T cells, not just antibodies, if we want a complete picture of the vaccine response for those who have not had COIVD-19 and for those who have recovered from the disease,” said senior author E. John Wherry, Ph.D., chair of the Department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania. 

And while Wherry states more investigations need to be done about the efficacy of using T-cells as part of a targeted vaccine program, he is optimistic about the future, stating, “We need to do follow-up studies to confirm the longevity of the T-cell response to vaccination, but our results here support the idea that that response can be long-lasting.”

Philip Dormitzer, Vice President and Chief Scientific Officer at Pfizer Vaccines Research and Development, has a more muted response, stating, “We certainly take it [T-cell response] with a grain of salt.” 

As the Delta variant rampages though the world population and our hospitals stack up with patients battling COVID-19, it may be that grain of salt that ends this pandemic. 

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