Aswathy Narayanan[1], Shilpa Ray[2], Jan Vesterbacka[1,2], Giorgio Gabarrini[4], Yu Gao[5], Hans-Gustaf Ljunggren[5], Marcus Buggert[5], Soo Aleman[2,4], Anders Sönnerborg [1,2,3], Margaret Sällberg Chen[4] and Piotr Nowak[1,3]

Affiliates

[1] Department of Medicine Huddinge, Division of Infectious Diseases, Karolinska Institutet, Stockholm, Sweden [2] Department of Laboratory Medicine, Division of Clinical Microbiology, ANA Futura, Karolinska Institutet, Stockholm 141 52 Sweden. [3] Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden [4] Department of Dental Medicine [5] Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Background: The mRNA-based SARS-CoV-2 vaccines have proved their safety and clinical efficacy against coronavirus disease (COVID-19). Previous data have shown associations of the gut microbiome with HIV infection disease status and immune response to vaccinations in the general population. In this study, we aimed to investigate whether the baseline gut microbiome could predict immune responses to the BNT162b2 SARS-CoV-2 vaccine in people living with HIV (PLWH) and healthy controls (HC).

Methods: Feces samples were collected from PLWH (n=68) and healthy controls (n=75) at baseline, before the first BNT162b2 vaccine dose. The individuals were part of the COVAXID Clinical trial, where humoral and cellular responses to SARS-CoV-2 vaccination were evaluated on day 35 after the first vaccine dose. The microbiome was analysed by 16S rRNA sequencing on the DNA extracted from fecal samples. The obtained raw reads were pre-processed, and QIIME2 was used for microbiome analysis and taxonomy classification. Additionally, comprehensive bioinformatic tools were used to reveal the associations between SARS-CoV-2 antibody/spike CD4+ T cell responses and microbial taxa, clinical parameters such as age, gender, and length of antiretroviral treatment.

Results:
We found that HC had a significantly higher spike IgG SARS-CoV-2 antibody titer at day 35 as compared to PLWH. Interestingly, we observed that the individuals with higher antibody titers depicted a lower bacterial alpha diversity (richness, evenness) as compared to those with lower antibody titers. These differences were consistent within both the HC and the PLWH groups. The bacterial taxa of Lachnospira (p=0.039) and Agathobacter (p=0.027) were found to be significantly enriched in high responders, whereas Paraprevotella (p=0.026), Ruminococcaceae UCG-007 (p=0.032) and Lachnospiraceae UCG-008 (p=0.01) were significantly enriched in low responders. Additionally, the individuals with higher spike specific CD4+ T cell responses also demonstrated a similar trend with a reduced bacterial diversity compared to those with low spike CD4+ T cell responses. Furthermore, we found that age was an additional factor associated with alpha diversity of microbiome and antibody responses.

Conclusion: Our results show an association between gut microbiome diversity and spike IgG responses after COVID-19 vaccination. These findings were consistent in the whole cohort, albeit group differences between the microbiome compositions in PLWH and HC were observed. Additionally, we present that age is a strong factor associated with alpha diversity of the gut microbiome.