Table 1.
A Selection of Recent Evidence for the Potential Importance of Microbiota in Immunity to Vaccination
| Model | Vaccine | Host | Study Outcomes | Reference |
|---|---|---|---|---|
| Animal Studies |
TIV, OPV | Mice | TLR5-mediated sensing of flagellin from gut microbiota had an adjuvant effect on TIV and OPV. No effect with adjuvanted vaccines or live-attenuated yellow fever vaccine. | (Oh et al., 2014) |
| CT | Mice | The mucosal adjuvant activity of CT was mediated through the recognition of symbiotic bacteria by Nod2 in CD11c-expressing phagocytes. | (Kim et al., 2016a) | |
| BCG, MenB, MenC, PCV13, Hexa | Mice | Antibiotics-induced dysbiosis in infant (but not adult) mice leads to impaired antibody responses and elevated ex vivo cytokine recall responses. | (Lynn et al., 2018) | |
| TIV | Rhesus macaques | Subclinical CMV infection resulted in increase in butyrate-producing bacteria and lower antibody responses to influenza vaccination. | (Santos Rocha et al., 2018) | |
| Correlative human studies | RV | Ghanaian and Dutch infants | Microbiome composition was different between RV responders and non-responders. Ghanaian responders were more similar to Dutch infants than to non-responders. | (Harris et al., 2017) |
| RV | Pakistani and Dutch infants | RV response correlated with a higher relative abundance of bacteria belonging to Clostridium cluster XI and Proteobacteria. | (Harris et al., 2018a) | |
| RV, OPV | Indian infants | No differences in microbiome composition between RV responders and non-responders. Co-administered OPV reduced the response to RV. | (Parker et al., 2018) | |
| OPV | Indian infants | Enteric viruses have a greater impact on OPV response than the bacterial microbiota, especially for recent enterovirus infections. | (Praharaj et al., 2019) | |
| BCG, TT, HBV, OPV | Bangladeshi infants | High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and with higher CD4+ T cell and antibody responses 2 years after vaccination. | (Huda et al., 2014, 2019) | |
| HIV | Swiss adults | The immunogenicity of HIV vaccine was correlated with microbiota clusters. | (Cram et al., 2019) | |
| Causation studies in humans | OPV | Indian infants | Antibiotics did not improve the immunogenicity of OPV, despite the reduction of biomarkers of enteropathy and pathogenic intestinal bacteria. | (Grassly et al., 2016) |
| RV, Pneumo23, TT | Dutch adults | Narrow-spectrum antibiotics resulted in higher day-7 anti-RV IgA boosting and increased RV-antigen shedding but no different absolute titers. The antibiotics did not affect pneumococcal or TT vaccination. | (Harris et al., 2018b) | |
| TIV | American adults | Antibiotics-induced microbiome loss impaired antibody response in subjects with low pre-existing immunity. | (Hagan et al., 2019) |
TIV, trivalent inactivated influenza vaccine; OPV, oral polio vaccine; CT, cholera toxoid; BCG, Bacillus Calmette–Guérin; MenB, Bexsero meningococcal serogroup B vaccine; MenC, NeisVac-C meningococcal serogroup C vaccine; PCV13, the Prevenar 13-valent pneumococcal conjugate vaccine; Hexa, the INFANRIX Hexa combination vaccine, which contains antigens from hepatitis B, diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, and inactivated poliomyelitis virus; RV, rotavirus vaccine; TT, tetanus toxoid; HBV, hepatitis B vaccine; Pneumo23, polysaccharide pneumococcal vaccine.