An influenza vaccine trial in human volunteers has generated results that could help scientists develop a universal influenza vaccine that offers broad protection against yearly shifting viral strains. In the small-scale Phase I study, a group 2 subtype H7N9 vaccine generated high levels of memory B cells that recognized the conserved stem region of both group 1 and group 2 influenza virus hemagglutinin (HA) proteins.

The influenza virus’ HA surface protein is a key target for neutralizing antibodies that destroy the virus, but seasonal flu vaccines induce B-cell responses that primarily target the highly variable, strain-specific head domain of the HA protein. Far fewer antibodies target the more conserved stem domain, yet it is these antibodies that have previously been found to exhibit broad neutralization of multiple influenza virus subtypes across groups.

An international team of researchers led by Sarah F. Andrews and Adrian B. McDermott, Ph.D., at the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) carried out two open-label Phase I trials in 40 volunteers to directly compare B-cell responses following immunization using either a group 1 H5N1 vaccine, or a group 2 H7N9 vaccine. The results showed that the group 2 H7N9 vaccine induced stem-targeted memory B cells that recognized both group 1 and group 2 virus subtypes. In contrast, the group 1 H5N1 vaccine induced B cells that specifically recognized group 1 virus subtypes. The group 2 H7N9 vaccine-induced B cells also produced HA stem-targeting antibodies against the two virus types at a much higher frequency than did the group 1 H5N1 vaccine-induced B cells.

“These data suggest that a group 2–based stem immunogen could prove more effective than a group 1 immunogen at eliciting broad cross-group protection in humans,” the authors conclude in their published paper, released today in Science Immunology. The paper is titled, “Preferential Induction of Cross-Group Influenza A Hemagglutinin Stem-Specific Memory B Cells after N7N9 Immunization in Humans.”

The researchers do point out that the two trials were conducted five years apart and involved relatively few volunteers, who were all in the U.S. “To further substantiate that group 2 subtypes universally elicit a broader response than group 1 subtypes in adults, these studies will need to be conducted with larger cohorts from diverse areas of the world with different influenza exposure histories,” they stress. “Large epidemiological studies tracing influenza exposure with repertoire and experimental clinical vaccine trials will continue to shed light on the best strategy for developing an HA stem–based universal influenza vaccine.”




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