How the Gut Microbiota Affects COVID-19 Vaccine Immunogenicity

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Gut microbial abundance was observed to be independent of age and influenced COVID-19 spike IgG levels.

Gut microbial abundance was observed to be independent of age and influenced COVID-19 spike IgG levels.

Since the commercial rollout of COVID-19 vaccines, there have been concerns that the vaccines will be less effective in immunocompromised persons, such as people living with HIV (PLWH).

PLWH have historically mounted a poor immunogenic response to various oral and parenteral vaccines. Now that the gut microbiome is being investigated for its influence on vaccine efficacy, one study became the first to examine whether the baseline gut microbiota can predict immune responses to the Pfizer-BioNTech (BNT162b2) COVID-19 vaccine in PLWH.

The study was presented by Piotr Nowak, of the Karolinska Institutet in Sweden, at the recent 30th Conference on Retroviruses and Opportunistic Infections (CROI 2023). At baseline, Nowak and fellow investigators performed 16S rRNA sequencing on DNA extracted from the fecal samples of 68 PLWH and 75 controls.

On day 35 after the first dose of Pfizer-BioNTech, the investigators evaluated humoral and cellular responses to the COVID-19 vaccine. They utilized comprehensive bioinformatic tools for bacterial identification, revealing the associations between gut microbiota, COVID-19 antibody, and spike CD4+ T-cell responses. The investigators also considered clinical parameters including age, gender, CD4/CD8 ratio, and length of antiretroviral therapy (ART).

At 30 days after vaccination, the healthy controls showed demonstrably higher spike IgG titers than the PLWH. The study authors noted that both phylogenetic and α-diversity were negatively correlated with antibody titers. Participants with lower α-diversity in the gut had higher levels of high spike IgG titers and spike-specific CD4+ T-cell responses.

Agathobacter, Lactobacillus, Bacteroides, and Lachnospira were positively correlated with both antibody levels and spike-specific CD4+ T-cell responses while Methanobrevibacter, Marvinbryantia, Cloacibacillus, and Succinivibrio had a negative correlation.

The results showed that PLWH and elderly persons mounted less of an immune response to Pfizer-BioNTech vaccination. However, independent of age, there was a significant association of bacterial abundance with IgG levels.

Bacterial diversity was lower in participants with higher spike IgG titers and higher spike-specific CD4+ T-cell response. These results may inspire further research into microbiome predictors of poor vaccine immune response.

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