The gut microbe pair of Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270 confers complete protection against SARS-CoV-2 infection by activating CD8+ T cell-mediated immunity

ABSTRACT

Despite the potential protective role of the gut microbiome against COVID-19, specific microbes conferring resistance to COVID-19 have not yet been identified. In this work, we aimed to identify and validate gut microbes at the species level that provide protection against SARS-CoV-2 infection. To identify gut microbes conferring protection against COVID-19, we conducted a fecal microbiota transplantation (FMT) from an individual with no history of COVID-19 infection or immunization into a lethal COVID-19 hamster model. FMT from this COVID-19-resistant donor resulted in significant phenotypic changes related to COVID-19 sensitivity in the hamsters. Metagenomic analysis revealed distinct differences in the gut microbiome composition among the hamster groups, leading to the identification of two previously unknown bacterial species: Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, both associated with COVID-19 resistance. Subsequently, we conducted a proof-of-concept confirmation animal experiment adhering to Koch’s postulates. Oral administration of this gut microbe pair, Oribacterium sp. GMB0313 and Ruminococcus sp. GMB0270, to the hamsters provided complete protection against SARS-CoV-2 infection through the activation of CD8+ T cell mediated immunity. The prophylactic efficacy of the gut microbe pair against SARS-CoV-2 infection was comparable to, or even superior to, current mRNA vaccines. This strong prophylactic efficacy suggests that the gut microbe pair could be developed as a host-directed universal vaccine for all betacoronaviruses, including potential future emerging viruses.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• gut microbiome
• host-directed vaccine
• CD8+ T cell
• universal vaccine
• betacoronavirus

Acknowledgments

This research was supported by SNJ Pharma Inc. We also appreciate the efforts of Jinki Hong (Lake Forest Academy, Lake Forest, IL) in collecting fecal samples.

Disclosure statement

This research is sponsored in part by SNJ Pharma Inc, in which HJK has a business and/or financial interest. The funders had no role in design of the study; or in the collection, analyzes, or interpretation of data. The funders had a role in the decision to publish the results.

Authors contributions

STH was responsible for the overall content as guarantor. STH and HJK conceived the research and designed the experiment; STH supervised the project; MW, EL, SK, CZ, and MMI performed the experiments and data curation; STH and HJK wrote the manuscript. All authors approved the final manuscript.

Availability of data and materials

Sequence data generated in this study was uploaded to the NCBI SRA database. It can be accessed via the accession number PRJNA1011488. The data that support the findings of this study are available on request from the corresponding author, Seong-Tshool Hong, upon reasonable request.

Ethics approval and consent to participate

All strategies including the mice and hamsters were authorized with the endorsement of the Institutional Animal Care and Use Committee (IACUC), in compliance with the rules of the Morals Committee of Jeonbuk National University (NON 2022 102) Research Facility Creature Center Rules on the Care and Utilize of Creatures for Logical Purposes. All animal experiments were done in accordance with the ARRIVE guideline and checklist to ensure compliance with ethical and scientific standards.

All the materials and procedures used in this study were handled in consistent manner with the guidelines provided by the CDC/ABSA/WHO for the prevention of human disease associated with SARS-CoV-2 infection.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2342497

Additional information

Funding

This research was funded by SNJ Pharma Inc (Program number: SNJ201).