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  1. Article ; Online: Enhanced inhibition of MHC-I expression by SARS-CoV-2 Omicron subvariants.

    Moriyama, Miyu / Lucas, Carolina / Monteiro, Valter Silva / Iwasaki, Akiko

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 16, Page(s) e2221652120

    Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By ... ...

    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 but not influenza virus infection in vivo. While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC-I, the Omicron subvariants exhibited a greater ability to suppress surface MHC-I expression. We identified a common mutation in the E protein of Omicron that further suppressed MHC-I expression. Collectively, our data suggest that in addition to escaping from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition.
    MeSH term(s) Humans ; Antibodies, Neutralizing ; Antibodies, Viral ; Breakthrough Infections ; COVID-19/genetics ; Reinfection ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2023-04-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2221652120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition.

    Moriyama, Miyu / Lucas, Carolina / Monteiro, Valter Silva / Iwasaki, Akiko

    bioRxiv : the preprint server for biology

    2022  

    Abstract: SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8 : ... ...

    Abstract SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8
    Summary: Moriyama et al. demonstrate that SARS-CoV-2 variants of concern retain similar MHC-I downregulation capacity compared to the ancestral virus. The results suggest that MHC-I evasion capacity is optimized in the ancestral virus and thus further adaptation was not observed.
    Language English
    Publishing date 2022-05-16
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2022.05.04.490614
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Contributions of maternal and fetal antiviral immunity in congenital disease.

    Yockey, Laura J / Lucas, Carolina / Iwasaki, Akiko

    Science (New York, N.Y.)

    2020  Volume 368, Issue 6491, Page(s) 608–612

    Abstract: Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections ... ...

    Abstract Viral infections during pregnancy can have devastating consequences on pregnancy outcomes, fetal development, and maternal health. In this review, we examine fetal and maternal immune defense mechanisms that mediate resistance against viral infections and discuss the range of syndromes that ensue when such mechanisms fail, from fetal developmental defects to establishment of chronic infection. Further, we highlight the role of maternal immune activation, or uncontrolled inflammation triggered by viral infections during pregnancy, and its potential downstream pathological effects, including tissue damage and fetal demise. Insights into the respective contributions of direct viral toxicity versus fetal and maternal immune responses that underlie the pathogenesis of congenital disease will guide future treatment strategies.
    MeSH term(s) Female ; Fetal Development/immunology ; Fetal Diseases/immunology ; Fetal Diseases/virology ; Fetus/abnormalities ; Fetus/immunology ; Fetus/virology ; Humans ; Immunity, Innate ; Maternal-Fetal Exchange/immunology ; Pregnancy ; Pregnancy Complications, Infectious/virology ; Pregnancy Outcome ; Virus Diseases/immunology
    Keywords covid19
    Language English
    Publishing date 2020-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.aaz1960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 27: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
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    Zs.MG 77: Show issues

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  4. Article: Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5.

    Fang, Zhenhao / Monteiro, Valter S / Hahn, Anne M / Grubaugh, Nathan D / Lucas, Carolina / Chen, Sidi

    Cell discovery

    2022  Volume 8, Issue 1, Page(s) 108

    Language English
    Publishing date 2022-10-11
    Publishing country England
    Document type Letter
    ISSN 2056-5968
    ISSN 2056-5968
    DOI 10.1038/s41421-022-00473-4
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  5. Article ; Online: SARS-CoV-2 variants do not evolve to promote further escape from MHC-I recognition

    Moriyama, Miyu / Lucas, Carolina / Monteiro, Valter Silva / Iwasaki, Akiko

    bioRxiv

    Abstract: SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T ... ...

    Abstract SARS-CoV-2 variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that VOCs retain similar MHC-I downregulation capacity compared to the ancestral virus. However, VOCs exhibit a greater ability to suppress type I IFN than the ancestral virus. Although VOCs possess unique mutations within the ORF8 gene, which suppresses MHC-I expression, none of these mutations enhanced the ability of ORF8 to suppress MHC-I expression. Notably, MHC-I upregulation was strongly inhibited after the ancestral SARS-CoV-2 infection in vivo. Collectively, our data suggest that the ancestral SARS-CoV-2 already possesses an intrinsically potent MHC-I evasion capacity, and that further adaptation by the variants was not observed.
    Keywords covid19
    Language English
    Publishing date 2022-05-04
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2022.05.04.490614
    Database COVID19

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  6. Article ; Online: Polyvalent mRNA vaccination elicited potent immune response to monkeypox virus surface antigens.

    Fang, Zhenhao / Monteiro, Valter S / Renauer, Paul A / Shang, Xingbo / Suzuki, Kazushi / Ling, Xinyu / Bai, Meizhu / Xiang, Yan / Levchenko, Andre / Booth, Carmen J / Lucas, Carolina / Chen, Sidi

    Cell research

    2023  Volume 33, Issue 5, Page(s) 407–410

    MeSH term(s) Animals ; Monkeypox virus ; Macaca fascicularis ; Immunity ; Vaccination
    Language English
    Publishing date 2023-03-06
    Publishing country England
    Document type Letter ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1319303-x
    ISSN 1748-7838 ; 1001-0602
    ISSN (online) 1748-7838
    ISSN 1001-0602
    DOI 10.1038/s41422-023-00792-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5283: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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  7. Article ; Online: Associations of SARS-CoV-2 serum IgG with occupation and demographics of military personnel.

    Zell, Joseph / Wisnewski, Adam V / Liu, Jian / Klein, Jon / Lucas, Carolina / Slade, Martin / Iwasaki, Akiko / Redlich, Carrie A

    PloS one

    2021  Volume 16, Issue 8, Page(s) e0251114

    Abstract: Background: Countries across the globe have mobilized their armed forces in response to COVID-19, placing them at increased risk for viral exposure. Humoral responses to SARS-CoV-2 among military personnel serve as biomarkers of infection and provide a ... ...

    Abstract Background: Countries across the globe have mobilized their armed forces in response to COVID-19, placing them at increased risk for viral exposure. Humoral responses to SARS-CoV-2 among military personnel serve as biomarkers of infection and provide a basis for disease surveillance and recognition of work-related risk factors.
    Methods: Enzyme-linked immunosorbent assays (ELISA) were used to measure SARS-CoV-2 spike antigen-specific IgG in serum obtained from N = 988 US National Guard soldiers between April-June 2020. Occupational information, e.g. military operating specialty (MOS) codes, and demographic data were obtained via questionnaire. Plaque assays with live SARS-CoV-2 were used to assess serum neutralizing capacity for limited subjects (N = 12).
    Results: The SARS-CoV-2 IgG seropositivity rate among the study population was 10.3% and significantly associated with occupation and demographics. Odds ratios were highest for those working in MOS 2T-Transportation (3.6; 95% CI 0.7-18) and 92F-Fuel specialist/ground and aircraft (6.8; 95% CI 1.5-30), as well as black race (2.2; 95% CI 1.2-4.1), household size ≥6 (2.5; 95% CI 1.3-4.6) and known COVID-19 exposure (2.0; 95% CI 1.2-3.3). Seropositivity tracked along major interstate highways and clustered near the international airport and the New York City border. SARS-CoV-2 spike IgG+ serum exhibited low to moderate SARS-CoV-2 neutralizing capacity with IC50s ranging from 1:15 to 1:280. In limited follow-up testing SARS-CoV-2 serum IgG levels remained elevated up to 7 months.
    Conclusions: The data highlight increased SARS-CoV-2 seroprevalence among National Guard vs. the local civilian population in association with transportation-related occupations and specific demographics.
    MeSH term(s) Adolescent ; Adult ; Aged ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; COVID-19/diagnosis ; COVID-19/epidemiology ; COVID-19/virology ; Demography ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin G/blood ; Male ; Middle Aged ; Military Personnel ; Odds Ratio ; SARS-CoV-2/isolation & purification ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Immunoglobulin G ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-08-30
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0251114
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  8. Article: Sex differences in symptomatology and immune profiles of Long COVID.

    Silva, Julio / Takahashi, Takehiro / Wood, Jamie / Lu, Peiwen / Tabachnikova, Alexandra / Gehlhausen, Jeff R / Greene, Kerrie / Bhattacharjee, Bornali / Monteiro, Valter Silva / Lucas, Carolina / Dhodapkar, Rahul M / Tabacof, Laura / Peña-Hernandez, Mario / Kamath, Kathy / Mao, Tianyang / Mccarthy, Dayna / Medzhitov, Ruslan / van Dijk, David / Krumholz, Harlan M /
    Guan, Leying / Putrino, David / Iwasaki, Akiko

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 ... ...

    Abstract Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection
    Language English
    Publishing date 2024-03-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.29.24303568
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  9. Article ; Online: Impact of B.1.1.7 variant mutations on antibody recognition of linear SARS-CoV-2 epitopes

    Haynes, Winston A. / Kamath, Kathy / Lucas, Carolina / Shon, John / Iwasaki, Akiko

    medRxiv

    Abstract: In 579 COVID patient samples collected between March and July of 2020, we examined the effects of non-synonymous mutations harbored by the circulating B.1.1.7 strain on linear antibody epitope signal for spike glycoprotein and nucleoprotein. At the ... ...

    Abstract In 579 COVID patient samples collected between March and July of 2020, we examined the effects of non-synonymous mutations harbored by the circulating B.1.1.7 strain on linear antibody epitope signal for spike glycoprotein and nucleoprotein. At the antigen level, the mutations only substantially reduced signal in 0.5% of the population. Although some epitope mutations reduce measured signal in up to 6% of the population, these are not the dominant epitopes for their antigens. Given dominant epitope patterns observed, our data suggest that the mutations would not result in immune evasion of linear epitopes for a large majority of these COVID patients.
    Keywords covid19
    Language English
    Publishing date 2021-01-08
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.01.06.20248960
    Database COVID19

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  10. Article ; Online: SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity.

    Jaycox, Jillian R / Lucas, Carolina / Yildirim, Inci / Dai, Yile / Wang, Eric Y / Monteiro, Valter / Lord, Sandra / Carlin, Jeffrey / Kita, Mariko / Buckner, Jane H / Ma, Shuangge / Campbell, Melissa / Ko, Albert / Omer, Saad / Lucas, Carrie L / Speake, Cate / Iwasaki, Akiko / Ring, Aaron M

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 1299

    Abstract: mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody ... ...

    Abstract mRNA-based vaccines dramatically reduce the occurrence and severity of COVID-19, but are associated with rare vaccine-related adverse effects. These toxicities, coupled with observations that SARS-CoV-2 infection is associated with autoantibody development, raise questions whether COVID-19 vaccines may also promote the development of autoantibodies, particularly in autoimmune patients. Here we used Rapid Extracellular Antigen Profiling to characterize self- and viral-directed humoral responses after SARS-CoV-2 mRNA vaccination in 145 healthy individuals, 38 patients with autoimmune diseases, and 8 patients with mRNA vaccine-associated myocarditis. We confirm that most individuals generated robust virus-specific antibody responses post vaccination, but that the quality of this response is impaired in autoimmune patients on certain modes of immunosuppression. Autoantibody dynamics are remarkably stable in all vaccinated patients compared to COVID-19 patients that exhibit an increased prevalence of new autoantibody reactivities. Patients with vaccine-associated myocarditis do not have increased autoantibody reactivities relative to controls. In summary, our findings indicate that mRNA vaccines decouple SARS-CoV-2 immunity from autoantibody responses observed during acute COVID-19.
    MeSH term(s) Humans ; Antibodies, Viral/immunology ; Autoantibodies/immunology ; Autoimmune Diseases/immunology ; Autoimmunity/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/therapeutic use ; Drug-Related Side Effects and Adverse Reactions/immunology ; Immunity, Humoral/immunology ; Myocarditis/immunology ; RNA, Messenger ; SARS-CoV-2 ; Vaccination ; Vaccines, Synthetic/adverse effects ; Vaccines, Synthetic/immunology ; Vaccines, Synthetic/therapeutic use ; mRNA Vaccines/adverse effects ; mRNA Vaccines/immunology ; mRNA Vaccines/therapeutic use
    Chemical Substances Antibodies, Viral ; Autoantibodies ; COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Synthetic ; mRNA Vaccines
    Language English
    Publishing date 2023-03-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36686-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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