Broad-Spectrum and Gram-Negative-Targeting Antibiotics Differentially Regulate Antibody Isotype Responses to Injected...

Area of Science:

• Immunology
• Microbiology
• Pharmacology

Background:

• Antibiotics are widely used for infections and frequently alter the gut microbiota.
• Understanding how antibiotics affect immune responses to vaccines is crucial.

Purpose of the Study:

• To investigate the differential regulation of systemic and mucosal immune responses to vaccines by broad-spectrum and Gram-negative-targeting antibiotics.
• To explore the role of the gut microbiota in shaping these immune responses.

Main Methods:

• Mice were immunized systemically with a model polyvalent vaccine after antibiotic treatment.
• Serum immunoglobulin (Ig) G1 and IgA levels were measured.
• Intestinal IgA antibody-secreting cells were quantified.
• Gut microbiota composition was analyzed using 16S rRNA sequencing.

Main Results:

• Antibiotic treatment enhanced serum IgG1 responses, dependent on vaccine antigen immunogenicity.
• Both broad-spectrum and Gram-negative-targeting antibiotics increased serum IgA and intestinal IgA antibody-secreting cells.
• Antibiotics altered the gut microbiota, reducing Firmicutes and increasing Bacteroidetes, with Proteobacteria increasing after broad-spectrum treatment.
• Enhanced mucosal IgA responses were not linked to increased gut-homing receptors on peripheral cells.

Conclusions:

• Oral antibiotic administration differentially regulates immunoglobulin isotype and subclass responses.
• The gut microbiota composition significantly shapes mucosal antibody responses following systemic immunization.
• Antibiotic-induced changes in the gut microbiome may impact vaccine efficacy.