COVID-19 vaccine-induced antibody response is associated with oral microbiota composition in patients with inflammatory bowel disease, cirrhosis, and liver transplantation

Introduction

The microbiota shapes host immune responses at mucosal barrier surfaces and the oral microbiota have been associated with COVID-19 outcomes. We explored the hypothesis that the salivary microbiota are associated with attenuated humoral response to SARS-CoV-2 vaccination in immunocompromised individuals, including inflammatory bowel disease (IBD), cirrhosis and orthotopic liver transplant (OLT) patients.

Methods

16S rRNA gene amplicon sequencing was performed on salivary DNA collected in the prospective multi-centre OCTAVE trial. Saliva was collected at baseline (BL), pre-second vaccine dose (Pre-V2) and 28 days post-second vaccine dose (V2+28). Anti-SARS-CoV-2 spike (S) immunoassay was used to measure antibody (Ab) response in serum at 28 days following two doses of Oxford/Astra Zeneca vaccine. Poor response was defined as anti-S Ab concentration <380AU/ml.

Results

293 saliva samples were collected from 126 patients (69 IBD, 31 cirrhosis, 26 OLT; median age 47 [range 21–73]; 7 with prior COVID-19). 47 patients had poor humoral response. Longitudinally, alpha diversity was significantly increased at pre-V2 and V2+28 compared to BL in IBD (p<0.04). In IBD, higher relative abundance of salivary Mycoplasma at BL was associated with good response (q<0.0001); at pre-V2, higher relative abundance of seven amplicon sequence variants (ASVs) was associated with good response, including two from genus Prevotella (both q<0.007). In cirrhosis, at pre-V2, relative abundance of 10 ASVs was associated with poor response, while higher relative abundance of 27 ASVs was associated with good response, including potential oral pathobionts; this included ASVs from genera Neisseria and Veillonella (both q<0.0001), and 7 ASVs from genus Prevotella (q<0.0001). In OLT, lower relative levels of 24 ASVs was associated with good response, and higher relative abundance of 5 ASVs at pre-V2 was associated with good response. These included notable bacteria from genera associated with periodontal disease including Abiotrophia and Lautropia (q<0.006).

Conclusions

We have found an association between the salivary microbiota and humoral response to vaccination in immunocompromised patients. Oral pathobionts associated with outcomes from COVID-19 (including Neisseria and Prevotella) may play an adjuvant role in priming COVID-19 vaccine-induced immunity.