Modulation of porcine alphacoronavirus pathogenesis by antibodies to SARS-CoV-2
- Authors: Nefedeva M.V.1, Titov I.A.1, Katorkin S.A.1, Tsybanov S.Z.1, Lyska V.M.1, Sereda A.D.1, Malogolovkin A.S.1,2,3
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Affiliations:
- Federal Research Center for Virology and Microbiology
- Sirius University of Science and Technology
- Sechenov First Moscow State Medical Univesity
- Issue: Vol 22, No 2 (2022)
- Pages: 221-228
- Section: Conference proceedings
- Published: 06.11.2022
- URL: https://journals.eco-vector.com/MAJ/article/view/108729
- DOI: https://doi.org/10.17816/MAJ108729
- ID: 108729
Cite item
Abstract
BACKGROUND: A variety of antibodies against the SARS-CoV-2 with different functional activities can lead to immune pathology and/or modulation of infection due to antibody-dependent enhancement. An important role in the development of ADE, as exemplified by Dengue fever, is played by low-affinity antibodies, which interacting with the virus, do not neutralize it, but on the contrary forms the virus-antibody complex to immune cells (monocytes/macrophages, B-cells). There are conflicting data on the antibody-dependent enhancement presence in COVID-19 coronavirus infection. Some studies indicate a relationship between the severity of infection in patients infected by SARS-СoV-2 and the level of antibodies to closely related coronaviruses.
AIM: The aim of the study was to understand the possibility of interaction between antibodies to SARS-CoV-2 with closely related porcine coronavirus (alphacoronavirus) and their ability to modulate the development of infection in vitro.
MATERIALS AND METHODS: In the study serums and leukocytes from patients, who are convalescent after COVID-19 infection in 2020, was used. Antibody titers (IgG/IgM) was checked by commercial kit (VektorBest, Russia), based on ELISA method. In the eukaryotic expression system — Chinese hamster ovary cells, monoclonal antibody to SARS-CoV-2 spike protein and its Fab version without Fc domain were obtained. As a model, swine alphacoronavirus- transmissible gastroenteritis virus (TGEV) was used. Replication activity of TGEV was studied in porcine leukocyte cell culture. The ability of this virusto induce the interferon gamma synthesis in leukocytes from convalescents was assessed TigraTest SARS-CoV-2 Enzyme-Linked SPOT analysis (Russia). Virus titration and neutralization assay with sera and monoclonal antibodies were carried out in porcine kidney PK-15 cell line.
RESULTS: Serum samples from 43 donors (59% female, 41% male) aged from 21 to 56 was studied for the presence of class M and G antibodies to SARS-CoV-2 by ELISA method. Class M antibodies were found in only one donor. The highest titers of class G antibodies (>1:400 to >1:1600) were detected among donors 40–50 years old. For four donors with the highest antibody titers, HLA-II type was determined. The DQA1 allele in 3 patients was found to have the *0501 variant, which, according to literature data, is associated with autoimmune thyroid diseases. For the DQB1 allele, two convalescents had exactly the same variants (*0602-8). Among HLA DRB1, all patients had different allele variants (*09, *11, *01,*03,*13,*15,*08,*13).
Among the samples, studied by ELISPOT method, in 45,5% of samples a positive T-cell response was noted after stimulation of macrophages with the S peptides of the SARS-CoV-2 protein and in 22.7% of samples in response to the pool of N peptides of the SARS-CoV-2 protein. Interestingly, infection of macrophages from convalescents with the transmissible gastroenteritis virus caused interferon-gamma expression in 31,8% of cases.
The monoclonal antibody to the Spike protein SARS-CoV-2 and its Fab variant were not able to neutralize the TGEV. Interestingly, serum samples from 16 donor’s convalescent after COVID-19 caused virus neutralization in PK-15 cell culture at dilutions of 1:4-1:8.
CONCLUSIONS: We have shown that porcine alphacoronavirus induces (in 31.8% of cases) the synthesis of interferon gamma in macrophages of recovered afterCOVID-19 donors, which may indicate cross-recognition of the antigen of a closely related coronavirus. However, monoclonal antibodies against the Spike protein SARS-CoV-2 did not demonstrate to TGEV neutralization. In turn, the neutralization of the TGEV by sera from recovered COVID-19 donors suggests that not only Spike protein, but also other coronavirus antigens can play a significant role in antigenic imprinting and antibody-dependent enhancement of COVID-19.
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About the authors
Mariya V. Nefedeva
Federal Research Center for Virology and Microbiology
Email: masha67111@mail.ru
ORCID iD: 0000-0002-6143-7199
SPIN-code: 2830-9043
Scopus Author ID: 57205706263
ResearcherId: L-7673-2016
Cand. Sci. (Biol.), Senior Research Associate
Russian Federation, VolginskyIlya A. Titov
Federal Research Center for Virology and Microbiology
Email: titoffia@yandex.ru
ORCID iD: 0000-0002-5821-8980
SPIN-code: 3432-8427
Scopus Author ID: 56494633200
Cand. Sci. (Biol.), Head of Laboratory
Russian Federation, VolginskySergey A. Katorkin
Federal Research Center for Virology and Microbiology
Email: katorkin2012@mail.ru
ORCID iD: 0000-0002-4844-9371
SPIN-code: 1378-9481
Cand. Sci. (Biol.), Junior Research Associate
Russian Federation, VolginskySodnom Zh. Tsybanov
Federal Research Center for Virology and Microbiology
Email: cybanov@mail.ru
ORCID iD: 0000-0001-8994-0514
SPIN-code: 4393-7819
Dr. Sci. (Biol.), Professor of the Research and Education Center
Russian Federation, VolginskyValentina M. Lyska
Federal Research Center for Virology and Microbiology
Email: vliska@yandex.ru
SPIN-code: 3833-7143
Cand. Sci. (Biol.), Head of Virology Unit
Russian Federation, VolginskyAlexey D. Sereda
Federal Research Center for Virology and Microbiology
Email: sereda-56@mail.ru
ORCID iD: 0000-0001-8300-5234
SPIN-code: 2599-8510
ResearcherId: A-9115-2014
Dr. Sci. (Biol.), Professor, Chief Research Associate
Russian Federation, VolginskyAlexander S. Malogolovkin
Federal Research Center for Virology and Microbiology; Sirius University of Science and Technology; Sechenov First Moscow State Medical Univesity
Author for correspondence.
Email: malogolovkin@inbox.ru
ORCID iD: 0000-0003-1352-1780
SPIN-code: 9846-9838
Cand. Sci. (Biol.), Chief Research Associate
Russian Federation, Volginsky; Sochi; MoscowReferences
- Mosaad YM. Clinical role of human leukocyte antigen in health and disease. Scand J Immunol. 2015;82(4):283–306. doi: 10.1111/sji.12329
- Tirado SM, Yoon KJ. Antibody-dependent enhancement of virus infection and disease. Viral Immunol. 2003;16(1):69–86. doi: 10.1089/088282403763635465
- Takada A, Kawaoka Y. Antibody-dependent enhancement of viral infection: molecular mechanisms and in vivo implications. Rev Med Virol. 2003;13(6):387–398. doi: 10.1002/rmv.405
- Wen J, Cheng Y, Ling R, et al. Antibody-dependent enhancement of coronavirus. Int J Infect Dis. 2020;100:483–489. doi: 10.1016/j.ijid.2020.09.015
- Dustin ML. Complement receptors in myeloid cell adhesion and phagocytosis. Microbiol Spectr. 2016;4(6):10.1128/microbiolspec.MCHD-0034-2016. doi: 10.1128/microbiolspec.MCHD-0034-2016
- Taylor A, Foo SS, Bruzzone R, et al. Fc receptors in antibody-dependent enhancement of viral infections. Immunol Rev. 2015;268(1):340–364. doi: 10.1111/imr.12367
- Zellweger RM, Prestwood TR, Shresta S. Enhanced infection of liver sinusoidal endothelial cells in a mouse model of antibody-induced severe dengue disease. Cell Host Microbe. 2010;7(2):128–139. doi: 10.1016/j.chom.2010.01.004
- Balsitis SJ, Williams KL, Lachica R, et al. Lethal antibody enhancement of dengue disease in mice is prevented by Fc modification. PLoS Pathog. 2010;6(2):e1000790. doi: 10.1371/journal.ppat.1000790
- Shim BS, Kwon YC, Ricciardi MJ, et al. Zika virus-immune plasmas from symptomatic and asymptomatic individuals enhance zika pathogenesis in adult and pregnant mice. mBio. 2019;10(4):e00758–19. doi: 10.1128/mBio.00758-19
- Slon Campos JL, Poggianella M, Marchese S, et al. DNA-immunisation with dengue virus E protein domains I/II, but not domain III, enhances Zika, West Nile and Yellow Fever virus infection. PloS One. 2017;12(7):e0181734. doi: 10.1371/journal.pone.0181734
- Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies. Nat Microbiol. 2020;5(10):1185–1191. doi: 10.1038/s41564-020-00789-5
- Ricke DO. Two different antibody-dependent enhancement (ADE) risks for SARS-CoV-2 antibodies. Front Immunol. 2021;12:640093. doi: 10.3389/fimmu.2021.640093
- Halstead SB, Katzelnick L. COVID-19 Vaccines: Should we fear ADE? J Infect Dis. 2020;222(12):1946–1950. doi: 10.1093/infdis/jiaa518
- Zhou Y, Liu Z, Li S, et al. Enhancement versus neutralization by SARS-CoV-2 antibodies from a convalescent donor associates with distinct epitopes on the RBD. Cell Rep. 2021;34(5):108699. doi: 10.1016/j.celrep.2021.108699
- García-Nicolás O, V’kovski P, Zettl F, et al. No evidence for human monocyte-derived macrophage infection and antibody-mediated enhancement of SARS-CoV-2 infection. Front Cell Infect Microbiol. 2021;11:644574. doi: 10.3389/fcimb.2021.644574
- Wan Y, Shang J, Sun S, et al. Molecular mechanism for antibody-dependent enhancement of coronavirus entry. J Virol. 2020;94(5):e02015–19. doi: 10.1128/JVI.02015-19
- Matsuyama S, Ujike M, Morikawa S, et al. Protease-mediated enhancement of severe acute respiratory syndrome coronavirus infection. Proc Natl Acad Sci USA. 2005;102(35):12543–12547. doi: 10.1073/pnas.0503203102
- Wang SF, Tseng SP, Yen CH, et al. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins. Biochem Biophys Res Commun. 2014;451(2):208–214. doi: 10.1016/j.bbrc.2014.07.090
- Jaume M, Yip MS, Cheung CY, et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway. J Virol. 2011;85(20):10582–10597. doi: 10.1128/JVI.00671-11
- Gavor E, Choong YK, Er SY, et al. Structural basis of SARS-CoV-2 and SARS-CoV antibody interactions. Trends Immunol. 2020;41(11):1006–1022. doi: 10.1016/j.it.2020.09.004