In a study with implications for the development of new influenza vaccine strategies, researchers discovered that – among patients who received the 2009 H1N1 influenza vaccine – individuals with low levels of H1N1-specific antibodies prior to vaccination produced a more broadly protective immune response against the influenza virus than patients with high levels of H1N1-specific antibodies prior to vaccination.
A research team led by Patrick C. Wilson, Ph.D., of the Knapp Center for Lupus and Immunology Research at the University of Chicago, studied the B cell response in patients who received the pandemic 2009 H1N1 vaccine 2 years in a row and had varied histories of influenza exposure. All patients were 18 years or older, healthy, and had not received the yearly influenza vaccine prior to participating in the study. The researchers compared the patients’ “vaccine-induced plasmablast response upon first vaccination with the pandemic H1N1 strain in 2009-2010” with the patients’ plasmablast response upon revaccination with this same strain in 2010-2011 or 2011-2012. Each of the 21 study participants provided the researchers with at least four H1N1-specific plasmablasts.
CDC/Cynthia Goldsmith
This highly magnified, digitally colorized transmission electron micrograph depicted numbers of virions from a novel flu H1N1 isolate.
The researchers “analyzed the immunoglobulin regions, strain specificity, and functional properties of the antibodies produced by this plasmablast population at the single-cell level across multiple years,” which allowed them to directly evaluate the effect of immune memory on the specificity of the current response to the virus.
Among the study’s findings was that “only individuals with low preexisting serological levels of pandemic H1N1 specific antibodies generated a broadly neutralizing plasmablast response directed toward the [hemagglutinin] stalk,” which is part of the hemagglutinin protein located on the surface of the influenza virus.
“[W]e demonstrate that the immune subdominance of the [hemagglutinin] stalk is a function of both the poor accessibility to the broadly protective epitopes and the inherent polyreactivity of the antibodies that can bind. We conclude that immunological memory profoundly shapes the viral epitopes targeted upon exposure with divergent influenza strains and determines the likelihood of generating a broadly protective response,” said Dr. Wilson and his coauthors. The authors reported no conflicts of interest.
Read the full study in Science Translational Medicine (doi: 10.1126/scitranslmed.aad0522).