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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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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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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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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 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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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
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Zs.A 5283: Show issues

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Article: Sex differences in symptomatology and immune profiles of Long COVID.

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
Database	MEDical Literature Analysis and Retrieval System OnLINE

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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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Article: Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2.

Fang, Zhenhao / Peng, Lei / Lucas, Carolina / Lin, Qianqian / Zhou, Liqun / Yang, Luojia / Feng, Yanzhi / Ren, Ping / Renauer, Paul A / Monteiro, Valter S / Hahn, Anne M / Park, Jonathan J / Zhou, Xiaoyu / Grubaugh, Nathan D / Wilen, Craig B / Chen, Sidi

Cell discovery

2022 Volume 8, Issue 1, Page(s) 69

Language	English
Publishing date	2022-07-19
Publishing country	England
Document type	Journal Article
ISSN	2056-5968
ISSN	2056-5968
DOI	10.1038/s41421-022-00435-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Grady, Connor B / Bhattacharjee, Bornali / Silva, Julio / Jaycox, Jillian / Lee, Lik Wee / Monteiro, Valter Silva / Sawano, Mitsuaki / Massey, Daisy / Caraballo, César / Gehlhausen, Jeff R / Tabachnikova, Alexandra / Mao, Tianyang / Lucas, Carolina / Peña-Hernandez, Mario A / Xu, Lan / Tzeng, Tiffany J / Takahashi, Takehiro / Herrin, Jeph / Güthe, Diana Berrent /

Akrami, Athena / Assaf, Gina / Davis, Hannah / Harris, Karen / McCorkell, Lisa / Schulz, Wade L / Grffin, Daniel / Wei, Hannah / Ring, Aaron M / Guan, Leying / Cruz, Charles Dela / Iwasaki, Akiko / Krumholz, Harlan M

medRxiv : the preprint server for health sciences

2024

Abstract: Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in ... ...

Abstract	Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-β and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.
Language	English
Publishing date	2024-01-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.11.24300929
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract.

Mao, Tianyang / Kim, Jooyoung / Peña-Hernández, Mario A / Valle, Gabrielee / Moriyama, Miyu / Luyten, Sophia / Ott, Isabel M / Gomez-Calvo, Maria Luisa / Gehlhausen, Jeff R / Baker, Emily / Israelow, Benjamin / Slade, Martin / Sharma, Lokesh / Liu, Wei / Ryu, Changwan / Korde, Asawari / Lee, Chris J / Silva Monteiro, Valter / Lucas, Carolina /

Dong, Huiping / Yang, Yi / Gopinath, Smita / Wilen, Craig B / Palm, Noah / Dela Cruz, Charles S / Iwasaki, Akiko

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

2024 Volume 121, Issue 18, Page(s) e2319566121

Abstract: Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that ... ...

Abstract	Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections.
MeSH term(s)	Animals ; Neomycin/pharmacology ; Neomycin/administration & dosage ; Administration, Intranasal ; Mice ; Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/administration & dosage ; SARS-CoV-2/immunology ; SARS-CoV-2/drug effects ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19/virology ; Respiratory Tract Infections/immunology ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/virology ; Respiratory Tract Infections/prevention & control ; Nasal Mucosa/immunology ; Nasal Mucosa/virology ; Nasal Mucosa/drug effects ; Disease Models, Animal ; COVID-19 Drug Treatment ; Mesocricetus ; Female ; Influenza A virus/drug effects ; Influenza A virus/immunology
Chemical Substances	Neomycin (I16QD7X297) ; Antiviral Agents
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; 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.2319566121
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