Researchers have discovered why different people’s immune systems target the same parts of a virus, which could help with the development of vaccines to target infections such as COVID-19.
Antibodies can be created against virtually any protein, yet people will often mount a response to the same protein regions—or epitopes—of a particular pathogen.
The investigators found that recognition of these immunodominant epitopes is driven by antibody regions called germline-encoded amino acid binding (GRAB) motifs.
Antibody responses to an epitope require a certain threshold of binding energy and GRAB motifs may provide a substantial proportion of this, the team reports in the journal Science.
The findings could help explain why viruses such as COVID-19 are able to reinfect people with prior immunity.
“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,” explained lead author Ellen Shrock, PhD, from Harvard Medical School in Boston, Massachusetts.
The researchers previously developed a tool called VirScan that enabled the identification of antiviral antibody epitopes.
Earlier findings showed that individuals often recognized viral peptides in a way that was relatively specific to that person. However, many other peptides—which the team terms “public epitopes”—were recognized by at least 98 per cent people seropositive for the given virus.
For their current study, the investigators used VirScan to analyze 569 blood samples from individuals in the U.S., Peru, and France.
They then mapped 376 immunodominant public epitopes from 51 viral species to determine where antibodies bound to their targets and found that germline-encoded sequences in antibodies drove recurrent recognition.
Antibody responses to publicly recognized peptides related to neither the age of the person nor their geographic location and appeared to be a general feature of the human antibody response.
Further analysis of antibody-antigen structures revealed 18 human and 21 partially overlapping mouse GRAB motifs within heavy and light V gene segments that in case studies proved critical for public epitope recognition.
“Our research may help explain a lot of the patterns we’ve seen during the COVID-19 pandemic, especially in terms of re-infection,” said corresponding author Stephen Elledge, PhD, also from Harvard Medical School.
He added: “Our findings could help inform immune predictions and may change the way people think about immune strategies.”
