Human antibodies targeting the same viral protein regions could be behind reinfection

Scientists have found that humans create antibodies targeting the same viral regions repeatedly, despite their ability to create a diverse repertoire of antibodies, and this, they say, could help explain a lot of reinfection patterns observed during the Covid-19 pandemic.

The team of investigators, led by those at Brigham and Women's Hospital (US), said that these "public epitopes", or the viral protein locations where the antibody recurrently attaches itself, suggested the ability of a virus to mutate a single amino acid to reinfect a population of previously immune hosts.

"Our findings could help inform immune predictions and may change the way people think about immune strategies," said corresponding author Stephen J. Elledge, professor of Genetics at Brigham.

Their findings have been published in the journal Science.

The investigators said that the studies so far had presented hints that people's immune systems didn't target epitopes at random and that there was a method to it.

They found in isolated examples of recurrent antibody responses across individuals. This meant that people recreated antibodies to home in on the same epitope, they said.

Antibodies are the Y-shaped sniffer dogs of the immune system that can find and flag foreign invaders.

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For this study, investigators analysed 569 blood samples from participants in the US, Peru, and France using VirScan, which can detect thousands of viral epitopes and give a snapshot of a person's immunological history from a single drop of blood.

They found that recognition of public epitopes was a general feature of the human antibody response.

They mapped 376 of these commonly targeted epitopes and found that antibodies recognised public epitopes through germline-encoded amino acid binding (GRAB) motifs - regions of the antibodies that are particularly good at picking out one specific amino acid.

So, instead of randomly choosing a target, human antibodies tend to focus on regions where these amino acids are available for binding, and thus repeatedly bind the same spots.

A small number of mutations can help a virus avoid being detected by these shared antibodies, allowing the virus to reinfect populations that were previously immune.

"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 of the Elledge lab.

The team further noted that while it is more likely for a person to produce antibodies against a public epitope, some people do produce rarer antibodies, which may more effectively protect them from reinfection.

These insights, they say, could have important implications for treatments developed against Covid-19, such as monoclonal antibodies, as well as for vaccine design.