Influenza vaccines elicit antibodies that protect against infection. A new study by Oh et al. shows that gut bacteria are required for optimal antibody responses to a flu vaccine in mice (Immunity 41, 478–492, 2014).
This group reported previously that Toll-like receptor 5 (TLR5) expression is increased in humans after vaccination with a trivalent inactivated influenza vaccine (TIV), and this induction correlates with antibody levels produced. Oh et al. now show that the influenza-specific antibody response to TIV is significantly reduced in Tlr5-deficient mice at 7 d and 84 d after vaccination, and again after a second vaccination, indicating an impaired memory response.
The authors hypothesized that flagellated bacteria are required to elicit optimal antibody responses to TIV, as flagellin is the ligand for TLR5. They showed that flu-specific antibody levels were reduced in germ-free mice after vaccination and restored by transfer of flagellated Escherichia coli. Antibiotic treatment also reduced antibody levels generated by the vaccine, which were restored by flagellated E. coli. Moreover, flagellin treatment increased the number of antibody-producing short-lived plasma cells and antibody levels produced by B cells in vitro. Mice with TLR5-deficient macrophages also had reduced antibody responses, suggesting that TLR5 signaling on multiple cell types is necessary for optimal humoral responses to TIV.
Understanding how high levels of antibodies are elicited by unadjuvanted vaccines such as TIV could help develop methods to improve vaccine efficacy.
About this article
Cite this article
Farrell, A. Vaccines: Bacteria improve vaccine responses. Nat Med 20, 1105 (2014). https://doi.org/10.1038/nm.3726