The waning effect of Covid-19 vaccines and the emergence of variants make it almost impossible to achieve herd immunity against the pandemic, and people will have to live with Covid-19 for a long time, skeptics say.

However, strategies focusing on T cell responses can help overcome the Covid-19 pandemic, researchers said in an immunology journal.

T cells are immune cells that directly kill virus-infected cells. Only T cells that recognize the virus are selectively activated when a person is infected with a virus. After T cells remove virus-infected cells, they remain as memory T cells.

Professor Shin Eui-cheol at the Graduate School of Medical Science and Engineering of the Korea Advanced Institute of Science and Technology (KAIST), professor Noh Ji-yun at the Department of Internal Medicine of Korea University College of Medicine, professor Jeong Hye-won at the Department of Internal Medicine of Chungbuk National University College of Medicine, and Jerome Kim, Director General of the International Vaccine Institute published a contribution article in an online edition of Nature Reviews Immunology.

The article is titled, “T cell-oriented strategies for controlling the COVID-19 pandemic.”

Nature Reviews Immunology is the most authoritative journal in immunology.

Covid-19 vaccines, including Pfizer, Moderna, and AstraZeneca vaccines, help produce neutralizing antibodies to prevent virus infection.

However, antibody titers tend to fall over time, and the vaccines’ effect is limited against the highly contagious Delta and Lambda variants.

In contrast, T cell immunity created after Covid-19 vaccination remains strong for a long time, which can prevent progression to severe Covid-19, the researchers said in the article.

“Although the kinetics of neutralizing antibodies titers vary among Covid-19 convalescent individuals, more than half of these individuals have waning levels of neutralizing antibodies after six months,” the article said. “Compared with neutralizing antibodies, SARS-CoV-2-specific memory T cells are maintained for a relatively long time.”

The researchers cited a study saying memory T cell responses in Covid-19 survivors were sustained for 10 months regardless of disease severity. The researchers noted that the memory T cell responses to the SARS (Severe Acute Respiratory Syndrome) virus, similar to the Covid-19 virus, were maintained for 17 years. The effect of T cell responses was conserved even against the Delta or Gamma variant.

“A practical goal may therefore be to reduce damage to public health by making COVID-19 a controllable disease, similar to influenza or the common cold,” the researchers said. “We, therefore, need to continue work on such vaccines that induce durable and broad protective T cell-mediated immunity against Covid-19.”

Some companies have begun clinical trials of Covid-19 vaccines that induce T cell immunity.

In Korea, Genexine and GeneOne Life Science are developing DNA Covid-19 vaccines GX-19N and GLS-5310, respectively. In Taiwan, Vaxxinity is developing a peptide-based vaccine, UB-612. In the U.S., Vaxart developed an oral Covid-19 vaccine VXA-CoV2-1 and is testing it in clinical trials.

The researchers said T cells could protect people from Covid-19 secondary to the activity of neutralizing antibodies. “Thus, sophisticated T cell-oriented vaccine strategies should be considered to control the Covid-19 pandemic in the longer term,” they emphasized.

In another contribution article for The Korean Doctors’ Weekly, a sister paper of Korea Biomedical Review, professor Shin said the severity and mortality of Covid-19 would significantly drop in vaccinated people.

Although neutralizing antibodies and memory T cells formed after vaccination cannot guarantee full protection against virus variants, they will work “to a certain degree,” he said.

Most breakthrough infections are mild cases because of the same reason, Shin went on to say.

“No matter how severe the mutation gets, it is impossible to completely evade the memory T cell response by mutating all of the T cell antigen epitopes scattered throughout the protein antigens at once,” he said.