Gut Microbiome: Predictor for COVID-19 Vaccine Response and Safety (CZ02 and BNT162b2)

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INFECTIOUS DISEASE

Medical writer: Christy Leung | Last updated: 29 April 2022 | In: COVID-19, SARS-CoV2, Pneumonia, Infectious Disease

Article Keywords

BNT162b2, SARS-CoV-2, CZ02, gut microbiome, vaccine response, antibodies, COVID-19

The first case of SARS-CoV-2 infection causing Coronavirus Disease 2019 (COVID-19) was reported in November 2019; it was not until December 2020 when the first COVID-19 vaccine was authorised for emergency use.¹ Following population-wide administration of vaccines, the proportion of hospitalised and ICU-admitted COVID-19 cases have reduced.² However, vaccine hesitancy concerning the safety profiles and efficacy of vaccines remains a public health concern.³The gut microbiome is known to interact with infection and immunity, such as immune response after BCG vaccine and COVID-19 disease prognosis.^4,5 Investigators are thus interested to learn whether certain gut microbiome composition can be prognostic indicators for adverse event occurrence and vaccine efficacy.

A local observational study was conducted to investigate the immunogenicity of the COVID-19 vaccines offered in Hong Kong, namely CZ02 (inactivated) vaccine and BNT162b2 (mRNA) vaccine.⁶ All 138 volunteer subjects were never diagnosed with COVID-19; 37 and 101 of them were then administered with two doses of CZ02 and BNT162b2 vaccines respectively. Immunogenicity was measured by the antibody levels in SARS-CoV-2 surrogate viral neutralisation test (sVNT) and spike receptor-binding domain (RBD) IgG ELISA one month after the second dose of vaccine, compared to baseline measurement. The microbes abundant in high-responders and subjects experiencing fewer post-vaccination adverse events were then identified by stool metagenomic sampling.

The immunogenicity of CZ02 vaccines was lower than that of BNT162b2 vaccines, as evidenced by sVNT values of 57.6% versus 95.2% (p<0.001) and anti-RBD values of 1725.0 versus 8696.0 (p<0.001).⁶ Vaccinees’ level of response was measured according to their sVNT levels; for BNT162b2 vaccinees, those with top 25% sVNT levels were classified as “highest-tier responders”.

High abundance of Bifidobacterium adolescentis was significantly predictive of high vaccine response for both CZ02 and BNT162b2, while Eubacterium rectale and Roseburia faecis were highly abundant specifically in BNT162b2 highest-tier responders.⁶ B. adolescentis, E. rectale and R. faecis all produce butyric acid, a short-chain fatty acid (SCFA); B. adolescentis also produces acetic and propionic acids.⁷ SCFAs produced increase the metabolic rate within B cells, releasing more energy to support plasma B cell differentiation for greater amount of antibody secretion.⁸ This accounts for the greater immune response in corresponding subjects, reflected by their higher sVNT and anti-RBD levels.

Meanwhile, subjects who experienced fewer adverse effects had greater abundance of Prevotella copri, Megamonas funiformis and Meganomas hypermegale.⁶ P. copri modulates bile acid metabolism; the bile acid metabolite produced facilitates differentiation of regulatory T (Treg) cells, possibly explaining the anti-inflammatory effect for fewer adverse effects.⁹ M. hypermegale is known to maintain a balance between Treg and Th17 cell activity.⁶

The findings mark an advancement in knowledge since April 2020, when the authors Francis Chan and Siew Ng stated that probiotics should not be used until the interaction between SARS-CoV-2 and gut microbiota is better understood.¹⁰ Understanding the role of B. adolescentis has inspired investigators to create a probiotic formula, marketed to augment vaccine efficacy.¹¹ Combined with prior knowledge that CZ02 vaccine is associated with fewer adverse events but less immunogenic than BNT162b2,¹²taking the probiotic formula may be a solution for those who opt for CZ02 vaccination but hope to mount sufficient immunogenicity.

Reference

Carvalho et al. Nature Reviews Immunology. 2021;21:245–

Moghadas et al. Clinical Infectious Diseases. 2021;73(12):2257–2264.

Wang et al. Frontiers in Public Health. 2021. doi: 10.3389/fpubh.2021.793533

Yeoh et al. Gut. 2021;70:698–706

Nadeem et al. Frontiers in Immunology. 2020. doi: 10.3389/fimmu.2020.00726

Ng et al. Gut. 2022;0:1–11.

Venegas et al. Frontiers in Immunology. 2019. doi: 10.3389/fimmu.2019/00277

Kim et al. Cell Host & Microbe. 2016;20(2):202–

Petakh et al. Viruses. 2022 Mar; 14(3): 477.

Mak et al. The Lancet Gastroenterology & Hepatology. 2020;5(7):644–

South China Morning Post. Coronavirus: gut bacteria can help boost antibody response to Covid-19 vaccines, Hong Kong study shows. Available at: https://www.scmp.com/news/hong-kong/health-environment/article/3158173/coronavirus-gut-bacteria-can-help-boost-antibody (Accessed 11 April 2022).

Peng et al. eBioMedicine – The Lancet Discovery Science. 2022;77:103904.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).