Researchers discover web-like antibody that could lead to needle-free COVID-19 vaccines

Researchers at McMaster University have uncovered a web-like antibody response that they say could help with the design of future COVID-19 vaccines.

The study, published in Proceedings of the National Academy of Sciences of the United States of America, looked at Immunoglobulin A (IgA) antibodies, which are found in the lungs, intestines and other areas of the body.

This is important because SARS-COV-2, a respiratory virus, usually enters the lungs first.

Understanding how those antibodies respond to viruses could help to develop needle-free vaccines that use a nasal spray or are inhaled, said Matthew Miller, the lead author and an associate professor at McMaster University's Michael G. DeGroote Institute for Infectious Disease Research.

"The way that antibodies that are most prevalent in our blood, called IgG antibodies, do that is fairly well understood," Miller said.

"But we don't know a lot about how blood cells in our mucosal surfaces, like our lungs and other intestines, are able to talk to other cells in the immune system."

To understand how these antibodies work, Miller and a team of researchers from McMaster and Western University studied the blood of human volunteers and analyzed their antibody response to influenza vaccinations and infections from COVID-19.

They found thatIgA antibodiesbind to a virus and help neutrophils, the most abundant white blood cell type, to detect the virus, according to Miller.

"When our neutrophils see the virus with these IgA antibodies bound to it, [they] essentially explode and release all of the DNA in the cell," he said. "What that creates is something that literally looks and acts like a sticky spider web."

This prevents the virus from spreading further, and then molecules in the spider web kill the virus once it is trapped, he said.

Researchers working on an inhaled COVID-19 vaccine

Understanding how IgA antibodies work can then help scientists develop avaccinethat would elicit that response, Miller said.

Miller and a team of collaborators are themselves working on avaccinethat wouldbe inhaled. They hopeto start Phase 1 clinical trials before the end of 2021, he said.

There are already precedents for these types of vaccines. For example, an influenza vaccine called FluMist is administered to children with a nasal spray.

"Those types of vaccines do a really good job at stimulating the immune responses in the lung that are very strong," he said. That's the place where we first see the virus."

"We don't get infected through our arm. We get infected when we breathe the virus in."

It would be a more comfortable vaccine than a needle, and it could potentially provide broader protection against variants, he said.

Research could also lead to other COVID-19 drug treatments

Understanding how IgA antibodies workcan also help to treat people who are already infected with COVID-19. The immune response can make the disease worse if it is poorly regulated, and there's evidence that the IgA antibody response could be partly responsible, Miller said.

"If our immune system produces too much of them, it can also cause disease to get worse. We know that [for] people who were infected with COVID-19 but were never vaccinated, their lungs were full of these nets," he said. "We never really understood why exactly."

He said the neutrophil provides a potential explanation for the nets. In future, he and his research team would like to study whether there are methods for reducing the severity of that immune response.

"There are drugs that can be used to block these antibodies from talking to their receptors on immune cells, which might be an effective treatment if it's the case that in unvaccinated people, these nets make infections worse."

He said the most critical findings of the work was understanding how the immune response can be helpful or harmful depending on whether a person is vaccinated first.

"It's one of those parts of our physiology that is always about balance."