Public Epitopes, Mechanisms of COVID-19 Reinfection Explained


Worldwide, the human immune system tends to make the same antibodies when targeting viruses, which can modify their structure to avoid detection.

Investigators at Harvard have made a new discovery about COVID-19 reinfection patterns. Using a tool that projects a person’s immunologic history, the team determined that new variants of SARS-CoV-2 can escape human antibody detection to reinfect the host by mutating an amino acid. Findings were published in the journal Science.

Coronavirus Covid-19. Credit: Photocreo Bednarek -

Coronavirus Covid-19. Credit: Photocreo Bednarek -

“Our findings could help inform immune predictions and may change the way people think about immune strategies,” said study author Stephen J. Elledge, PhD, Gregor Mendel Professor of Genetics at the Brigham and Harvard Medical School (HMS), in a press release.

Isolated examples suggest that antibodies—Y-shaped structures that are created to target and defend against viruses—bind to amino acids at the same epitope, or region of a viral protein. However, not enough evidence confirms that the immune system calculably targets certain parts of a virus, according to investigators. The current study aimed to explain this mechanism and examine human antibody response.

Investigators collected 569 blood samples using VirScan, a tool that can detect viral epitopes through blood samples and map a person’s immunological history. Collecting blood samples from people around the world (United States, Peru, and France), investigators discovered that all human antibodies can also recognize public epitopes, or regions of a viral protein that are recurrently targeted by antibodies.

The antibody, which uses germline-encoded amino acid binding (GRAB) motifs to recognize amino acids on the viral region, will continually bind to these amino acids because they are readily available. When the next generation of antibodies is created, they will only recognize the amino acids in this same region of the virus. Therefore, if the virus were to mutate even a single amino acid, the resulting variant could evade current immune antibodies to reinfect the host.

“We find an underlying architecture in the immune system that causes people, no matter where in the world they live, to make essentially the same antibodies that give the virus a very small number of targets to evade in order to reinfect people and continue to expand and further evolve,” said lead author Ellen L. Shrock, PhD, Elledge lab, in the press release.

Nonhuman species can produce antibodies that recognize varying public epitopes. There are certain people who produce rare antibodies that are better equipped to defend against reinfection, but most people produce antibodies that only fight against 1 specific public epitope.

Investigators suggest that the findings could change the understanding of immunity, public health, and could be used to develop COVID-19 treatments, including monoclonal antibodies or a different vaccine design.

“The more unique antibodies may be a lot harder to evade, which is important to consider as we think about the design of better therapies and vaccines,” Elledge said in the press release.


Brigham and Women’s Hospital. Researchers Reveal Why Viruses Like SARS-CoV-2 Can Reinfect Hosts, Evade the Immune Response. Newswise. April 6, 2023. Accessed April 7, 2023.

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