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Article ; Online: mRNA Vaccine-Elicited Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Specific T Cells Persist at 6 Months and Recognize the Delta Variant.

Woldemeskel, Bezawit A / Garliss, Caroline C / Blankson, Joel N

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 75, Issue 1, Page(s) e898–e901

Abstract: Little is known about the decay kinetics of coronavirus disease 2019 vaccine-elicited severe acute respiratory syndrome coronavirus 2-specific T cells. In this study we show a modest decline in the frequency of these T cells at 6 months and demonstrate ... ...

Abstract	Little is known about the decay kinetics of coronavirus disease 2019 vaccine-elicited severe acute respiratory syndrome coronavirus 2-specific T cells. In this study we show a modest decline in the frequency of these T cells at 6 months and demonstrate robust expansion in response to antigen and recognition of spike peptides from the Delta variant.
MeSH term(s)	Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; T-Lymphocytes ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; Vaccines, Synthetic ; mRNA Vaccines
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab915
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Article ; Online: SARS-CoV-2 mRNA vaccines induce broad CD4+ T cell responses that recognize SARS-CoV-2 variants and HCoV-NL63.

Woldemeskel, Bezawit A / Garliss, Caroline C / Blankson, Joel N

The Journal of clinical investigation

2021 Volume 131, Issue 10

Abstract: Recent studies have shown T cell cross-recognition of SARS-CoV-2 and common cold coronavirus spike proteins. However, the effect of SARS-CoV-2 vaccines on T cell responses to common cold coronaviruses (CCCs) remains unknown. In this study, we analyzed ... ...

Abstract	Recent studies have shown T cell cross-recognition of SARS-CoV-2 and common cold coronavirus spike proteins. However, the effect of SARS-CoV-2 vaccines on T cell responses to common cold coronaviruses (CCCs) remains unknown. In this study, we analyzed CD4+ T cell responses to spike peptides from SARS-CoV-2 and 3 CCCs (HCoV-229E, HCoV-NL63, and HCoV-OC43) before and after study participants received Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) mRNA-based COVID-19 vaccines. Vaccine recipients showed broad T cell responses to the SARS-CoV-2 spike protein, and we identified 23 distinct targeted peptides in 9 participants, including 1 peptide that was targeted in 6 individuals. Only 4 of these 23 targeted peptides would potentially be affected by mutations in the UK (B.1.1.7) and South African (B.1.351) variants, and CD4+ T cells from vaccine recipients recognized the 2 variant spike proteins as effectively as they recognized the spike protein from the ancestral virus. Interestingly, we observed a 3-fold increase in the CD4+ T cell responses to HCoV-NL63 spike peptides after vaccination. Our results suggest that T cell responses elicited or enhanced by SARS-CoV-2 mRNA vaccines may be able to control SARS-CoV-2 variants and lead to cross-protection against some endemic coronaviruses.
MeSH term(s)	Adult ; CD4-Positive T-Lymphocytes/immunology ; COVID-19 Vaccines/immunology ; Coronavirus 229E, Human/genetics ; Coronavirus 229E, Human/immunology ; Coronavirus NL63, Human/genetics ; Coronavirus NL63, Human/immunology ; Coronavirus OC43, Human/genetics ; Coronavirus OC43, Human/immunology ; Cross Reactions ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; BNT162 vaccine (N38TVC63NU)
Language	English
Publishing date	2021-04-06
Publishing country	United States
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI149335
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Article ; Online: Low neutralisation of the omicron BA.2 sublineage in boosted individuals who had breakthrough infections.

Karaba, Andrew H / Johnston, Trevor S / Aytenfisu, Tihitina Y / Woldemeskel, Bezawit A / Garliss, Caroline C / Cox, Andrea L / Blankson, Joel N

The Lancet. Microbe

2022 Volume 3, Issue 9, Page(s) e644

Language	English
Publishing date	2022-06-22
Publishing country	England
Document type	Letter ; Research Support, N.I.H., Extramural
ISSN	2666-5247
ISSN (online)	2666-5247
DOI	10.1016/S2666-5247(22)00180-X
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Article ; Online: Viral reservoirs in elite controllers of HIV-1 infection: Implications for HIV cure strategies.

Woldemeskel, Bezawit A / Kwaa, Abena K / Blankson, Joel N

EBioMedicine

2020 Volume 62, Page(s) 103118

Abstract: Elite controllers are HIV-1 positive subjects who control viral replication without antiretroviral therapy. Many of these subjects have replication-competent virus and thus represent a model of a functional cure. Peripheral CD4+ T cells in these subjects ...

Abstract	Elite controllers are HIV-1 positive subjects who control viral replication without antiretroviral therapy. Many of these subjects have replication-competent virus and thus represent a model of a functional cure. Peripheral CD4+ T cells in these subjects have small reservoirs with a low frequency of intact proviruses. Furthermore, recent studies suggest that many of these intact proviruses are disproportionally integrated at sites that have limited transcriptional activity raising the possibility that replication-competent viruses do not replicate because they are in a "blocked and locked" state. However, this feature is probably a consequence rather than a cause of elite control. Additionally, evolution of plasma virus has been detected in many elites suggesting that there continues to be ongoing viral replication in other compartments. While exceptional elite controllers with very limited viral reservoirs have recently been described, more work is needed to determine whether these patients have achieved a sterilizing cure.
MeSH term(s)	CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/virology ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/transmission ; HIV Infections/virology ; HIV-1/physiology ; Host-Pathogen Interactions ; Humans ; Proviruses ; Viral Load ; Virus Integration ; Virus Latency/drug effects ; Virus Replication/drug effects
Language	English
Publishing date	2020-11-10
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2020.103118
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Article ; Online: Discordant Antibody and T-Cell Responses to the Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant in Coronavirus Disease 2019 Messenger RNA Vaccine Recipients.

Woldemeskel, Bezawit A / Garliss, Caroline C / Aytenfisu, Tihitina Y / Johnston, Trevor S / Cox, Andrea L / Karaba, Andrew H / Blankson, Joel N

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 75, Issue 9, Page(s) 1652–1654

Abstract: We compared antibody and T-cell responses against the severe acute respiratory syndrome coronavirus 2 vaccine strain spike protein to responses against the Omicron variant in 15 messenger RNA vaccine recipients. While these individuals had significantly ... ...

Abstract	We compared antibody and T-cell responses against the severe acute respiratory syndrome coronavirus 2 vaccine strain spike protein to responses against the Omicron variant in 15 messenger RNA vaccine recipients. While these individuals had significantly lower levels of antibodies that inhibited Omicron spike protein binding to ACE2, there was no difference in T-cell responses.
MeSH term(s)	Humans ; COVID-19 Vaccines ; SARS-CoV-2/genetics ; RNA, Messenger/genetics ; COVID-19 ; T-Lymphocytes ; Antibodies, Viral ; Antibodies, Neutralizing ; mRNA Vaccines
Chemical Substances	COVID-19 Vaccines ; RNA, Messenger ; Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2022-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac305
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Article ; Online: Viral reservoirs in elite controllers of HIV-1 infection

Bezawit A. Woldemeskel / Abena K. Kwaa / Joel N. Blankson

EBioMedicine, Vol 62, Iss , Pp 103118- (2020)

Implications for HIV cure strategies

2020

Abstract	Elite controllers are HIV-1 positive subjects who control viral replication without antiretroviral therapy. Many of these subjects have replication-competent virus and thus represent a model of a functional cure. Peripheral CD4+ T cells in these subjects have small reservoirs with a low frequency of intact proviruses. Furthermore, recent studies suggest that many of these intact proviruses are disproportionally integrated at sites that have limited transcriptional activity raising the possibility that replication-competent viruses do not replicate because they are in a “blocked and locked” state. However, this feature is probably a consequence rather than a cause of elite control. Additionally, evolution of plasma virus has been detected in many elites suggesting that there continues to be ongoing viral replication in other compartments. While exceptional elite controllers with very limited viral reservoirs have recently been described, more work is needed to determine whether these patients have achieved a sterilizing cure.
Keywords	HIV ; Elite controllers ; HIV controllers ; Viremic controllers ; Reservoirs ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in diverse coronaviruses.

Woldemeskel, Bezawit A / Dykema, Arbor G / Garliss, Caroline C / Cherfils, Saphira / Smith, Kellie N / Blankson, Joel N

The Journal of clinical investigation

2022 Volume 132, Issue 5

Abstract: Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from ... ...

Abstract	Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera, including SARS-CoV, MERS-CoV, multiple bat coronaviruses, and a feline coronavirus. Our results showed that S815-827 was recognized by 42% of vaccinated participants in our study who received the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccines. Using T cell expansion and T cell receptor sequencing assays, we demonstrated that S815-827-reactive CD4+ T cells from the majority of responders cross-recognized homologous peptides from at least 6 other diverse coronaviruses. Our results support the hypothesis that the current mRNA vaccines elicit T cell responses that can cross-recognize bat coronaviruses and thus might induce some protection against potential zoonotic outbreaks. Furthermore, our data provide important insights that inform the development of T cell-based pan-coronavirus vaccine strategies.
MeSH term(s)	2019-nCoV Vaccine mRNA-1273/administration & dosage ; 2019-nCoV Vaccine mRNA-1273/immunology ; BNT162 Vaccine/administration & dosage ; BNT162 Vaccine/immunology ; CD4-Positive T-Lymphocytes/immunology ; COVID-19/immunology ; COVID-19/prevention & control ; Epitopes, T-Lymphocyte/immunology ; Female ; Humans ; Male ; Peptides/immunology ; Receptors, Antigen, T-Cell/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology
Chemical Substances	Epitopes, T-Lymphocyte ; Peptides ; Receptors, Antigen, T-Cell ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; 2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI156083
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Article ; Online: The BNT162b2 mRNA Vaccine Elicits Robust Humoral and Cellular Immune Responses in People Living With Human Immunodeficiency Virus (HIV).

Woldemeskel, Bezawit A / Karaba, Andrew H / Garliss, Caroline C / Beck, Evan J / Wang, Kristy H / Laeyendecker, Oliver / Cox, Andrea L / Blankson, Joel N

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 74, Issue 7, Page(s) 1268–1270

Abstract: Previous studies have shown that certain vaccines induce suboptimal responses in people living with human immunodeficiency virus (HIV, PLWH). However, responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have not been fully ... ...

Abstract	Previous studies have shown that certain vaccines induce suboptimal responses in people living with human immunodeficiency virus (HIV, PLWH). However, responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have not been fully characterized in these patients. Here we show that the BNT162b2 vaccine induces robust immune responses comparable to responses in healthy donors.
MeSH term(s)	Antibodies, Viral ; BNT162 Vaccine ; COVID-19/prevention & control ; HIV ; HIV Infections ; Humans ; Immunity, Cellular ; Immunity, Humoral ; SARS-CoV-2 ; Vaccines, Synthetic ; mRNA Vaccines
Chemical Substances	Antibodies, Viral ; Vaccines, Synthetic ; mRNA Vaccines ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab648
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Article ; Online: Decay of coronavirus disease 2019 mRNA vaccine-induced immunity in people with HIV.

Woldemeskel, Bezawit A / Karaba, Andrew H / Garliss, Caroline C / Beck, Evan J / Aytenfisu, Tihitina Y / Johnston, Trevor S / Laeyendecker, Oliver / Cox, Andrea L / Blankson, Joel N

AIDS (London, England)

2022 Volume 36, Issue 9, Page(s) 1315–1317

Abstract: Current coronavirus disease 2019 (COVID-19) mRNA vaccines induce robust SARS-CoV-2-specific humoral and cellular responses in people with HIV (PWH). However, the rate of decay of effector immune responses has not been studied in these individuals. Here, ... ...

Abstract	Current coronavirus disease 2019 (COVID-19) mRNA vaccines induce robust SARS-CoV-2-specific humoral and cellular responses in people with HIV (PWH). However, the rate of decay of effector immune responses has not been studied in these individuals. Here, we report a significant waning of antibody responses but persistent T-cell responses 6 months post vaccination in virally suppressed PWH with high CD4+ T-cell counts. These responses are comparable with those seen in healthy donors.
MeSH term(s)	Animals ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines ; HIV Infections ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; SARS-CoV-2 ; Vaccination ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Vaccines, Synthetic ; Viral Vaccines ; mRNA Vaccines
Language	English
Publishing date	2022-07-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003263
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Article ; Online: Proviral location affects cognate peptide-induced virus production and immune recognition of HIV-1-infected T cell clones.

Dragoni, Filippo / Kwaa, Abena K / Traut, Caroline C / Veenhuis, Rebecca T / Woldemeskel, Bezawit A / Camilo-Contreras, Angelica / Raymond, Hayley E / Dykema, Arbor G / Scully, Eileen P / Rosecrans, Amanda M / Smith, Kellie N / Bushman, Frederic D / Simonetti, Francesco R / Blankson, Joel N

The Journal of clinical investigation

2023 Volume 133, Issue 21

Abstract: BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that ... ...

Abstract	BACKGROUNDHIV-1-infected CD4+ T cells contribute to latent reservoir persistence by proliferating while avoiding immune recognition. Integration features of intact proviruses in elite controllers (ECs) and people on long-term therapy suggest that proviruses in specific chromosomal locations can evade immune surveillance. However, direct evidence of this mechanism is missing.METHODSIn this case report, we characterized integration sites and full genome sequences of expanded T cell clones in an EC before and after chemoradiation. We identified the cognate peptide of infected clones to investigate cell proliferation and virus production induced by T cell activation, and susceptibility to autologous CD8+ T cells.RESULTSThe proviral landscape was dominated by 2 large clones with replication-competent proviruses integrated into zinc finger (ZNF) genes (ZNF470 and ZNF721) in locations previously associated with deeper latency. A third nearly intact provirus, with a stop codon in Pol, was integrated into an intergenic site. Upon stimulation with cognate Gag peptides, infected clones proliferated extensively and produced virus, but the provirus in ZNF721 was 200-fold less inducible. While autologous CD8+ T cells decreased the proliferation of cells carrying the intergenic provirus, they had no effect on cells with the provirus in the ZNF721 gene.CONCLUSIONSWe provide direct evidence that upon activation of infected clones by cognate antigen, the lower inducibility of intact proviruses in ZNF genes can result in immune evasion and persistence.FUNDINGOffice of the NIH Director and National Institute of Dental & Craniofacial Research; NIAID, NIH; Johns Hopkins University Center for AIDS Research.
MeSH term(s)	Humans ; HIV-1 ; HIV Infections ; Proviruses/genetics ; CD4-Positive T-Lymphocytes ; Clone Cells ; Virus Latency
Language	English
Publishing date	2023-11-01
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI171097
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