Self-report. Several factors are known to play important roles in response to vaccines, such as age, medications, primary and secondary immunodeficiencies, and chronic diseases. The intestinal flora is also a factor that affects the immunogenicity of vaccines. Research shows that intestinal flora can influence the body's response to vaccinations, which can be seen in vaccination studies but also in the relationship between antibiotic treatment and the immune response. [1].

The Phase 4 Covaxid study is investigating response to the mRNA-based vaccine BNT162b2 in 5 groups of immunocompromised patients and in healthy controls (https://clinicaltrials.gov/study/NCT04780659). In our substudy, the effect of intestinal flora on the immune response to this vaccine was studied in 68 HIV-infected and 75 healthy subjects. In stool samples collected before vaccination, the microbiome was analyzed by 16S rRNA sequencing. The results were then linked to humoral and cellular immune responses 35 days after the first vaccine dose.

Results show that people with high IgG titers and highly specific CD4+ T cell responses against the SARS-CoV-2 protein had a less diverse gut microbiome before vaccination. [2]. This pattern was observed in all participants, regardless of whether they were HIV positive or healthy controls. At the genus level, Agathobacter, Lactobacillus, Bacteroides, and Lachnospira are positively associated with both spike protein IgG levels and protein-specific CD4+ T cell responses. Furthermore, network analysis showed that Bifidobacterium and Faecalibacterium were markers of a higher antibody response, while Cloacibacillus was associated with a lower antibody response. An interesting observation was that age had a clear effect on both the gut microbiome and vaccine response.

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Thus, our study demonstrates an important link between the gut microbiome and immune response to an mRNA-based SARS-CoV-2 vaccine. We would like to emphasize the need for continued research to understand these complex interactions and potential applications in clinical practice. The finding could play an important role in developing future strategies to improve vaccines, for example by modifying the microbiome using probiotics. This may be particularly important in target groups with a poor immune response to vaccination, such as immunocompromised patients and elderly individuals.