If Antibodies Fall Short of Covid-19 Immunity, Call the T-cells

Antibodies Alone Might Not be Enough

Many news headlines have reported that Covid-19 antibodies wane rather quickly. This statement is based on a China study published in Nature Medicine involving 37 symptomless and 37 symptomatic Covid-19 patients. Almost all of them showed over 70% decline in protective antibodies after two to three months. And, in that period, 40% of symptomless and 13% of symptomatic patients lost their antibodies completely.

A pre-print research with a larger sample size of 1500 persons tested positive for Covid-19 also derived at similar results. More than 10% no longer have protective antibodies after 21 days of disease onset. “After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus,” they closed.

This fading antibody immunity trend of Covid-19 is similar to that of previous coronaviruses. Antibodies against human coronavirus 229ESARS-CoV-1, and MERS-CoV all lasted for about a year only.

“After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.”

Even the blood plasma of recovered Covid-19 people do not have high antibody levels but is still sufficient to fend off the virus to some extent in vitro (cell culture in a laboratory petri dish), as shown by another June study in Nature Medicine. If the same translates to humans, then reduced antibodies might still be protective. But those having no antibodies at all would be susceptible to subsequent re-infections, which renders “immunity passports” or herd immunity strategies useless.

Vaccination Still Stand a Chance

While herd immunity or “immunity passports” are no longer feasible strategies, vaccination is still is. Vaccines can be designed to elicit the most robust immune response against the Covid-19 virus. So, vaccines stand a chance at generating better immunity than natural infections would.

“You can aim at inducing protection that would be better than what you would get from an infection,” Nicolas Vabret, an assistant professor of medicine who specializes in viral-immunology, commented. Akiko Iwasaki, a professor of many titles at Yale University, also agreed that potent vaccines are more important than ever. “Immunity that develops naturally during infection is suboptimal and short-lived in most people,” she told The New York Times. “We cannot rely on natural infection to achieve herd immunity.”

T-cells Might be the Missing Key

Most vaccines to date, however, rely on antibodies produced by B-cells. The aim is to prime the immune system to deploy a stronger antibody response to neutralize a specific infection before it causes symptoms. But what about the other branch of the adaptive immune system, T-cells?

“Most people are generally not aware of T-cell immunity, and so much of the conversation has focused on antibody levels.”

The adaptive immune system means it adapts. They mount immune responses catered to one specific infection and then remembers it. Vaccines work by exploiting the latter. And the adaptive immune system comprises B-cells (that produce antibodies) and T-cells (that kill infected cells and recruit other types of immune cells, including B-cells).

“Most people are generally not aware of T-cell immunity, and so much of the conversation has focused on antibody levels,” Angela Rasmussen, PhD, a virologist at Columbia University, told The New York Times yesterday in response to the fading antibodies against Covid-19. And, indeed, that’s where vaccine research is heading towards.

If B-cells’ antibodies are not enough, call the T-cells.

“Many newer vaccines and vaccines in development are often designed to generate T-cell responses that have the potential to help the antibody response, have direct effector functions themselves, or activate innate effector cells such as macrophages and neutrophils,” a 2018 review published in Vaccines stated. Why T-cells? As the report said, T-cells can enhance activities of B-cells and other immune cells, while having the ability to kill infected cells themselves. So, if B-cells’ antibodies are not enough, call the T-cells.

Good News is that SARS-CoV-2 Provokes T-cells

In May, the esteemed Cell journal published a paper titled, “Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals,” by twenty researchers at US institutions. The study showed that, in 20 recovered Covid-19 patients, everyone generated robust T-cells and antibodies immune responses.

“If we had seen only marginal immune responses, we would have been concerned,” Alessandro Sette, Professor and Member of the La Jolla Institute’s Infectious Disease and Vaccine Center, who led the Cell study said. “But what we see is a very robust T-cell response against the spike protein, which is the target of most ongoing Covid-19 efforts, as well as other viral proteins.”

Not all hope is lost if antibody responses are not enough. There is still another branch of the adaptive immune system called T-cells.

Professor Sette’s team research is backed by their bioinformatics analyses published back in April in Cell Host and Microbe — that the spike protein of SARS-CoV-2 is capable of activating human T-cells. And, indeed, nearly every vaccine in development targets that spike protein.

Another pre-print paper by over 60 researchers at the University of Oxford produced supporting results involving 28 mild and 14 severe Covid-19 patients who had recovered. Although both groups showed T-cells activation to the viral spike proteins, the severe group’s responses were greater.

Not all hope is lost if antibody responses to SARS-CoV-2 are not enough. There is still another branch of the adaptive immune system called T-cells.