People treated with an antibiotic before or while receiving a flu shot may have a weakened response to the vaccine, according to a new study with mice.
The findings, published in the journal Immunity, demonstrate a dependency on gut bacteria for strong immune responses to the seasonal flu and inactivated polio vaccines, and may also help explain why immunity induced by some vaccines varies in different parts of the world.
Antibody responses to vaccines containing immune stimulating substances called adjuvants were not affected by a lack of gut bacteria. For example, bacteria were not critical for responses to the Tdap (Tetanus-Diphtheria-Pertussis) vaccine.
“Our results suggest that the gut microbiome may be exerting a powerful effect on immunity to vaccination in humans, even immunity induced by a vaccine that is given at a distant site,” says Bali Pulendran, professor of pathology and laboratory medicine at Emory University School of Medicine and Yerkes National Primate Research Center.
The impetus for the research was a previous study involving an analysis of the immune response to influenza vaccination in humans, using the “systems vaccinology” approach, Pulendran says.
Critical ingredient: Flagella
Researchers had observed that in humans given the flu vaccine, the expression of the gene encoding TLR5 a few days after vaccination was correlated with strong antibody responses weeks later. TLR5 encodes a protein that enables immune cells to sense flagellin, the main structural protein for the whips (flagella) many bacteria use to propel themselves.
The ability of immune cells to sense flagellin appears to be the critical component affecting vaccine responses, the study shows. Mice lacking TLR5—but still colonized with bacteria—have diminished responses to flu vaccines, similar to antibiotic-treated or germ-free mice.
Oral reconstitution of antibiotic treated mice with bacteria containing flagellin, but not with mutant bacteria lacking flagellin, could restore the diminished antibody response.
“These results demonstrate an important role for gut bacteria in shaping immunity to vaccination, and raise the possibility that the microbiome could be harnessed to modulate vaccine efficacy,” says Pulendran. “The key question is the extent to which this impacts protective immunity in humans.”
Pulendran says that his team is planning a study in humans to address this issue.
The first author of the paper is postdoctoral fellow Jason Oh. Researchers at Georgia State University and University of North Carolina contributed to the paper.
The National Institute for Allergy and Infectious Diseases and the National Institute of Diabetes, Digestive, and Kidney Diseases supported the study.
Source: Emory University