Researchers plot first steps of flu antibody development

Scientists with the National Institutes of Health are mapping how a type of immature immune cell responds to the influenza virus to determine how the cells can create a wide range of antibodies.

The researchers hope to use the findings to develop universal flu vaccines that elicit antibodies to target the stem of hemagglutinin, an influenza protein. Standard vaccines target the variable head of the HA. Because the stem of the virus changes little from strain to strain, a universal vaccine could theoretically provide broad flu protection.

"This new understanding of how an immature immune cell transforms into a mature B cell capable of producing antibodies that neutralize a wide variety of influenza viruses could speed progress toward a universal flu vaccine - one that would provide protection against most or all influenza virus strains," Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said.

Gary Nabel, the leader of the study, and his team demonstrated that immature antibodies could only recognize and bind to the stem of HA when antibodies are attached to a naive B cell's membrane. A naive B cell is a precursor immune cell that can eventually become a producer of broadly neutralizing antibodies. When the immature antibodies attach to the naive B cell, the cell matures into numerous daughter cells, some of which have the genetic changes needed to bind to the stem of HA.

"We have repeated the first critical steps in the route leading to broadly neutralizing influenza antibodies," Nabel said. "Understanding how such antibodies originate could allow for rational design of vaccine candidates that would prompt the correct naive B cells to go on to mature into bnAb-producing cells."

Nabel said the findings could also have implications on the design of an HIV vaccine.

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