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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
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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: 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
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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
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Article ; Online: 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 /

medRxiv

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.
Keywords	covid19
Language	English
Publishing date	2024-01-12
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2024.01.11.24300929
Database	COVID19

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Article ; Online: Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination.

Pérez-Then, Eddy / Lucas, Carolina / Monteiro, Valter Silva / Miric, Marija / Brache, Vivian / Cochon, Leila / Vogels, Chantal B F / Malik, Amyn A / De la Cruz, Elena / Jorge, Aidelis / De Los Santos, Margarita / Leon, Patricia / Breban, Mallery I / Billig, Kendall / Yildirim, Inci / Pearson, Claire / Downing, Randy / Gagnon, Emily / Muyombwe, Anthony /

Razeq, Jafar / Campbell, Melissa / Ko, Albert I / Omer, Saad B / Grubaugh, Nathan D / Vermund, Sten H / Iwasaki, Akiko

Nature medicine

2022 Volume 28, Issue 3, Page(s) 481–485

Abstract: The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we ... ...

Abstract	The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.
MeSH term(s)	Antibodies, Neutralizing ; Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2/genetics ; Vaccination ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Vaccines, Synthetic ; mRNA Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-01705-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Distinguishing features of Long COVID identified through immune profiling.

Klein, Jon / Wood, Jamie / Jaycox, Jillian / Lu, Peiwen / Dhodapkar, Rahul M / Gehlhausen, Jeff R / Tabachnikova, Alexandra / Tabacof, Laura / Malik, Amyn A / Kamath, Kathy / Greene, Kerrie / Monteiro, Valter Silva / Peña-Hernandez, Mario / Mao, Tianyang / Bhattacharjee, Bornali / Takahashi, Takehiro / Lucas, Carolina / Silva, Julio / Mccarthy, Dayna /

Breyman, Erica / Tosto-Mancuso, Jenna / Dai, Yile / Perotti, Emily / Akduman, Koray / Tzeng, Tiffany J / Xu, Lan / Yildirim, Inci / Krumholz, Harlan M / Shon, John / Medzhitov, Ruslan / Omer, Saad B / van Dijk, David / Ring, Aaron M / Putrino, David / Iwasaki, Akiko

medRxiv : the preprint server for health sciences

2022

Abstract: SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long ... ...

Abstract	SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.08.09.22278592
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

Filardi, Bruno Andraus / Monteiro, Valter Silva / Schwartzmann, Pedro Vellosa / do Prado Martins, Vivian / Zucca, Luis Eduardo Rosa / Baiocchi, Gabriela Crispim / Malik, Amyn A / Silva, Julio / Hahn, Anne M / Chen, Nicholas F G / Pham, Kien / Pérez-Then, Eddy / Miric, Marija / Brache, Vivian / Cochon, Leila / Larocca, Rafael A / Mendez, Roberto Della Rosa / Bardini Silveira, Douglas / Pinto, Aguinaldo Roberto /

Science translational medicine

2023 Volume 15, Issue 683, Page(s) eade6023

Abstract: The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their ... ...

Abstract	The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.
MeSH term(s)	Humans ; Aged ; Antibody Formation ; BNT162 Vaccine ; COVID-19 ; SARS-CoV-2 ; Immunoglobulin G ; Antibodies, Viral
Chemical Substances	sinovac COVID-19 vaccine ; BNT162 Vaccine ; Immunoglobulin G ; Antibodies, Viral
Language	English
Publishing date	2023-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.ade6023
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Article ; Online: Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose

Filardi, Bruno Andraus / Monteiro, Valter Silva / Schwartzmann, Pedro Vellosa / Martins, Vivian do Prado / Rosa Zucca, Luis Eduardo / Baiocchi, Gabriela Crispim / Hahn, Anne M. / Chen, Nicholas / Pham, Kien / Perez-Then, Eddy / Miric, Marija / Brache, Vivian / Cochon, Leila / Larocca, Rafael / Yale SARS-CoV-2 Genomic Surveillance Initiative, / Mendez, Roberto Della Rosa / Silveira, Douglas Bardini / Pinto, Aguinaldo Roberto / Croda, Julio /

Yildirim, Inci / Omer, Saad B. / Ko, Albert / Vermund, Sten / Grubaugh, Nathan D / Iwasaki, Akiko / Lucas, Carolina

medRxiv

Abstract: The emergence of the SARS-CoV-2 Omicron sublineages resulted in drastically increased transmission rates and reduced protection from vaccine-induced immunity. To counteract these effects, multiple booster strategies were used in different countries, ... ...

Abstract	The emergence of the SARS-CoV-2 Omicron sublineages resulted in drastically increased transmission rates and reduced protection from vaccine-induced immunity. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remains sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed worldwide, particularly in China, and South America. However, whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses and whether these responses vary across age groups remain unknown. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals in central and south America that received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccines. We found that both IgG levels against SARS-CoV-2 spike or RBD, as well as neutralization titers against Omicron sublineages, were substantially reduced in participants that received homologous CoronaVac when compared to heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients older than 50 years of age. In this group, CoronaVac booster induced low virus-specific IgG levels and failed to elevate their neutralization titers against any omicron sublineage. Our results point to significant inefficiency in mounting protective anti-viral humoral immunity in those who were primed with CoronaVac followed by CoronaVac booster, particularly among older adults, urging a heterologous regimen in high-risk populations fully vaccinated with CoronaVac.
Keywords	covid19
Language	English
Publishing date	2022-10-06
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2022.10.04.22280704
Database	COVID19

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