Study reports first direct evidence of germinal center response in humans following influenza vaccination

NIAID CEIRS | Research Publication Commentary

Turner J et al. (2020) Human germinal centres engage memory and naive B cells after influenza vaccination. Nature.

While the race for a COVID-19 vaccine continues across the world, the annual flu season in the Northern Hemisphere is quietly approaching. Vaccine development remains a critical component in combating viral threats, including pandemic and seasonal influenza virus strains. The primary strategy deployed by current seasonal influenza vaccinations is to stimulate memory B cell-driven antibody production against circulating influenza virus strains. During the immune response to a viral infection, germinal centers (GC) within secondary lymphoid organs (such as lymph nodes or the spleen) are the sites where mature B cells proliferate and differentiate to become a cell that secretes antibodies. Currently, knowledge on the GC reaction to influenza vaccination, rather than natural infection, is relatively unclear. In their recently published article in Nature, CEIRS investigators demonstrated that influenza virus vaccination can induce a reaction in the GC, which increases the likelihood of B cell clone recruitment toward targeting novel influenza virus epitopes. These findings indicate the potential for broad-spectrum protection against influenza virus strains.

To determine the extent of quadrivalent inactivated influenza virus vaccine (QIV) induced B cell clone proliferation in the GC, individuals were vaccinated with the 2018/2019 seasonal QIV, and peripheral blood mononuclear cells (PBMC) and fine-needle aspirate (FNA) were sampled from lymph nodes to test for the GC response. PMBCs consist of several types of white blood cells, including lymphocytes and plasmablasts, that are important in vaccine response. FNA is a type of biopsy procedure that uses a thin needle to sample tissue or liquid; in this experiment, FNA samples of lymph nodes were taken from study participants. The PBMC and FNA samples were analyzed to see if the responding plasmablasts were similar to the B cells originating from the GC.

The investigators demonstrated the presence of B cells originating from a vaccine-induced GC reaction for up to 9 weeks in 3 of the 8 participants, including significant clonal overlap between early circulating plasmablasts and GC B cells. The monoclonal antibodies (mAbs) produced by these overlapping clones demonstrated broad cross-reactivity, though in some individuals, samples of vaccine-induced GC B cells did not display broadly cross-reactive properties and were likely instead strain-specific. The cross-reactivity of mAbs produced by overlapping GC B cells and plasmablasts pertains to previous exposure to circulating influenza virus strains.

This experiment aimed to analyze the role of the vaccine-induced GC reaction in human B cells, as this relationship was previously unexplored in humans. The investigators provide the first direct evidence of vaccine-induced GC response in humans; however, the investigators noted this response was not observed in the majority of participants. Further studies should be completed to investigate the significance of the vaccine-induced GC response in humans. The CEIRS investigators’ findings provides new insight into the influenza vaccine-induced immune response in humans and provides insight for future seasonal influenza vaccine development research, as researchers aim to develop vaccine formulations effective against a broader scope of emerging and circulating influenza virus strains.