COVID-19 Vaccination Alters NK Cell Dynamics and Transiently Reduces HBsAg Titers Among Patients With Chronic Hepatitis B

Overview

Journal Immune Netw

Specialty Allergy & Immunology

Date 2023 Nov 16

PMID 37970236

Authors

Hyunjae Shin

Ha Seok Lee

Ji Yun Noh

June-Young Koh

So-Young Kim

Jeayeon Park

Sung Won Chung

Moon Haeng Hur

Min Kyung Park

Yun Bin Lee

Yoon Jun Kim

Jung-Hwan Yoon

Jae-Hoon Ko

Kyong Ran Peck

Joon Young Song

Eui-Cheol Shin

Jeong-Hoon Lee

Affiliations

Soon will be listed here.

Abstract

Coronavirus disease 2019 (COVID-19) vaccination may non-specifically alter the host immune system. This study aimed to evaluate the effect of COVID-19 vaccination on hepatitis B surface Ag (HBsAg) titer and host immunity in chronic hepatitis B (CHB) patients. Consecutive 2,797 CHB patients who had serial HBsAg measurements during antiviral treatment were included in this study. Changes in the HBsAg levels after COVID-19 vaccination were analyzed. The dynamics of NK cells following COVID-19 vaccination were also examined using serial blood samples collected prospectively from 25 healthy volunteers. Vaccinated CHB patients (n=2,329) had significantly lower HBsAg levels 1-30 days post-vaccination compared to baseline (median, -21.4 IU/ml from baseline), but the levels reverted to baseline by 91-180 days (median, -3.8 IU/ml). The velocity of the HBsAg decline was transiently accelerated within 30 days after vaccination (median velocity: -0.06, -0.39, and -0.04 log IU/ml/year in pre-vaccination period, days 1-30, and days 31-90, respectively). In contrast, unvaccinated patients (n=468) had no change in HBsAg levels. Flow cytometric analysis showed that the frequency of NK cells expressing NKG2A, an NK inhibitory receptor, significantly decreased within 7 days after the first dose of COVID-19 vaccine (median, -13.1% from baseline; p<0.001). The decrease in the frequency of NKG2A NK cells was observed in the CD56CD16 NK cell population regardless of type of COVID-19 vaccine. COVID-19 vaccination leads to a rapid, transient decline in HBsAg titer and a decrease in the frequency of NKG2A NK cells.

References

De Maria A, Bozzano F, Cantoni C, Moretta L . Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 2010; 108(2):728-32. PMC: 3021076. DOI: 10.1073/pnas.1012356108. View

Andre P, Denis C, Soulas C, Bourbon-Caillet C, Lopez J, Arnoux T . Anti-NKG2A mAb Is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells. Cell. 2018; 175(7):1731-1743.e13. PMC: 6292840. DOI: 10.1016/j.cell.2018.10.014. View

Chung G, Kim J, Shin H, Hong J, Hur M, Cho H . Correlation between Results of Semi-Quantitative and Quantitative Tests for Hepatitis B Virus Surface Antigen among Patients Achieving Viral Suppression with Antiviral Treatment. Diagnostics (Basel). 2022; 12(7). PMC: 9317496. DOI: 10.3390/diagnostics12071757. View

Dagan N, Barda N, Kepten E, Miron O, Perchik S, Katz M . BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N Engl J Med. 2021; 384(15):1412-1423. PMC: 7944975. DOI: 10.1056/NEJMoa2101765. View

Tong S, Liu G, Li M, Li X, Liu Q, Peng H . Natural killer cell activation contributes to hepatitis B viral control in a mouse model. Sci Rep. 2017; 7(1):314. PMC: 5428210. DOI: 10.1038/s41598-017-00387-2. View

Creelan B, Antonia S . The NKG2A immune checkpoint - a new direction in cancer immunotherapy. Nat Rev Clin Oncol. 2019; 16(5):277-278. DOI: 10.1038/s41571-019-0182-8. View

Boettler T, Csernalabics B, Salie H, Luxenburger H, Wischer L, Salimi Alizei E . SARS-CoV-2 vaccination can elicit a CD8 T-cell dominant hepatitis. J Hepatol. 2022; 77(3):653-659. PMC: 9021033. DOI: 10.1016/j.jhep.2022.03.040. View

Zhang C, Wang X, Li S, Twelkmeyer T, Wang W, Zhang S . NKG2A is a NK cell exhaustion checkpoint for HCV persistence. Nat Commun. 2019; 10(1):1507. PMC: 6447531. DOI: 10.1038/s41467-019-09212-y. View

La Sala L, Gandini S, Bruno A, Allevi R, Gallazzi M, Senesi P . SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence. Front Immunol. 2022; 13:798813. PMC: 8882867. DOI: 10.3389/fimmu.2022.798813. View

10.

Efe C, Kulkarni A, Beretta-Piccoli B, Magro B, Stattermayer A, Cengiz M . Liver injury after SARS-CoV-2 vaccination: Features of immune-mediated hepatitis, role of corticosteroid therapy and outcome. Hepatology. 2022; 76(6):1576-1586. PMC: 9348326. DOI: 10.1002/hep.32572. View

11.

Li F, Wei H, Wei H, Gao Y, Xu L, Yin W . Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice. Gastroenterology. 2012; 144(2):392-401. DOI: 10.1053/j.gastro.2012.10.039. View

12.

Kim H, Jee Y, Song B, Shin J, Yang S, Mun H . Molecular epidemiology of hepatitis B virus (HBV) genotypes and serotypes in patients with chronic HBV infection in Korea. Intervirology. 2006; 50(1):52-7. DOI: 10.1159/000096313. View

13.

Moss P . The T cell immune response against SARS-CoV-2. Nat Immunol. 2022; 23(2):186-193. DOI: 10.1038/s41590-021-01122-w. View

14.

Rehermann B . Natural Killer Cells in Viral Hepatitis. Cell Mol Gastroenterol Hepatol. 2015; 1(6):578-588. PMC: 4678927. DOI: 10.1016/j.jcmgh.2015.09.004. View

15.

Lensen R, Netea M, Rosendaal F . Hepatitis C Virus Reactivation Following COVID-19 Vaccination - A Case Report. Int Med Case Rep J. 2021; 14:573-576. PMC: 8412816. DOI: 10.2147/IMCRJ.S328482. View

16.

Zin Tun G, Gleeson D, Al-Joudeh A, Dube A . Immune-mediated hepatitis with the Moderna vaccine, no longer a coincidence but confirmed. J Hepatol. 2021; 76(3):747-749. PMC: 8491984. DOI: 10.1016/j.jhep.2021.09.031. View

17.

Osawa Y, Ohtake T, Suto D, Akita T, Yamada H, Kohgo Y . Cases of Rapid Hepatitis B Surface Antigen Reduction after COVID-19 Vaccination. Intern Med. 2022; 62(1):51-57. PMC: 9876716. DOI: 10.2169/internalmedicine.0842-22. View

18.

Rowley M, Patel A, Zhou W, Wong M, Seetharam A . Immune Reconstitution Syndrome with Initiation of Treatment of HBV/HIV Co-infection: Activity Flare associated with E antigen Seroconversion. Ann Hepatol. 2019; 18(1):220-224. DOI: 10.5604/01.3001.0012.7918. View

19.

Yip T, Wong G, Chan H, Tse Y, Lam K, Lui G . HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues. J Hepatol. 2018; 70(3):361-370. DOI: 10.1016/j.jhep.2018.10.014. View

20.

Thomas D . Global Elimination of Chronic Hepatitis. N Engl J Med. 2019; 380(21):2041-2050. DOI: 10.1056/NEJMra1810477. View