NIH scientists report new insights into the workings of the immune system that may help in the development of a universal flu vaccine. Gary J. Nabel, M.D., and colleagues at the National Institutes of Allergy and Infectious Diseases (NIAID) Vaccine Research Center have effectively identified key stages in the development of antibody-producing B cells, by tracing back along the pathway by which immature B cells recognize the conserved stem region of the influenza virus hemagluttinin (HA) protein antigen and develop into mature cells that produce broadly neutralizing antibodies.
The team’s work has shown that germline-encoded precursors of these antibodies act as functional B-cell antigen receptors (BCRs) that trigger subsequent affinity maturation. However, key to this process is the observation that the immature antibodies will only recognize the HA stem when they are expressed as IgM molecules on the surface of the immature B cells, and not when present as soluble immunoglobulines (IgG). Contact between IgM and HA stem antigen then triggers maturation of the naive B cells into mature B cells that generate broadly neutralizing HA-stem-binding antibodies.
Reporting their findings in Nature, the researchers say understanding how such broadly neutralizing antibodies originate could help in the rational design of vaccine candidates that prompt the correct naive B cells to mature into broadly neutralizing antibody-producing cells. “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 towards a universal flu vaccine—one that would provide protection against most or all influenza virus strains,” concludes NIAID director Anthony S. Fauci, M.D.
Dr. Nabel et al., describe their results in a paper titled “Structural and genetic basis for development of broadly neutralizing influenza antibodies.”