Antibodies from the original strain of the virus that causes COVID-19, the one which started this pandemic, likely do not bind well to newer strains. The findings raise new concerns regarding emerging variants of the virus.
Research from the University of Illinois Urbana-Champaign reports that antibodies against the original coronavirus strain aren't that effective against some of the strains which developed later. The metastudy analyzed published studies to obtain patient data related to the sequence of antibodies they produced in response to the virus. These antibodies work by binding to, and thus neutralizing, the molecule that allows this virus to infect our cells -- a particular spike protein on its surface.
While the antibodies recorded so far in patients who fought off the infection worked well against the original coronavirus strain, they're not that effective in binding to emerging strains, the team explains. Understanding what kind of antibodies we naturally produce against a particular infection is a key step in the development of a vaccine, they add, so the results of this study could go a long way towards nipping a new pandemic in the bud.
Old dog, new tricks
"Antibody response is quite relevant to everything from understanding natural infection and how we recover from infection to vaccine design. The body has the capability to produce diverse antibody responses—it's estimated we could make a trillion different antibodies. So when you see people are making quite similar antibodies to a particular virus, we call it convergent antibody response," says Nicholas Wu, a professor of biochemistry at the University of Illinois, and lead author of the paper.
"That means we can design vaccines trying to elicit this kind of antibody response, and that is probably going to improve the responsiveness of more individuals to the vaccine."
The team reports that the antibody response to the original virus was consistent among patients. Two main groups of antibodies were identified from published literature on this topic, and both bound well to the virus' spike protein. Both were, also, quite effective in neutralizing the virus by targeting this protein. As such, our vaccines were also tailored to teach our bodies how to identify and attack the spike protein.
But the data gathered by the authors show that neither of these two groups of antibodies worked particularly well against newer variants of the virus. This has some pretty unpleasant implications for our current vaccines. As they are designed to coax our bodies into producing antibodies that attack the spike protein present on the original coronavirus, and these antibodies don't bind very well to new strains, we have cause to question how effective current vaccines are at stopping new strains. At the same time, the results point to a particular weakness in our defense, one we could, potentially, fix through the use of vaccine boosters or a similar approach. In epidemiology, "what I don't know can't hurt me" is an approach that will get you killed.
"We really focused on characterizing the antibodies created in those infected with the original strain of the virus," says graduate student Timothy Tan, the first author of the study. "Before we started the study, variants weren't much of a problem. As they emerged, we wanted to see whether the common antibodies we identified were able to bind to newer variants."
"Even though this antibody response is very common with the original strain, it doesn't really interact with variants," Wu said. "That, of course, raises the concern of the virus evolving to escape the body's main antibody response. Some antibodies should still be effective—the body makes antibodies to many parts of the virus, not only the spike protein—but the particular groups of antibodies that we saw in this study will not be as effective."
The team plans to extend their research to the antibody responses to the delta variant and other strains of the coronavirus. Their main objective is to see whether these strains also produce a convergent response in patients, and how the antibodies for these differ from the original strain
"We want to design vaccines and boosters, if needed, that can protect a majority of the population," Tan said. "We expect that the antibody response to those variants would be quite different. When we have more data about the antibodies of patients who have been infected with variants, understanding the difference in the immune response is one of the directions that we would like to pursue."
The paper "Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain" has been published in the journal Nature Communications.