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Article ; Online: Peripheral blood biomarkers predict viral rebound following antiretroviral therapy discontinuation in SIV-infected, early ART-treated rhesus macaques.

Aid, Malika / Colarusso, Alessandro / Walker-Sperling, Victoria / Barouch, Dan H

Cell reports. Medicine

2023 Volume 4, Issue 7, Page(s) 101122

Abstract: The discovery of biomarkers that predict viral rebound after discontinuation of antiretroviral therapy (ART) would significantly contribute to the HIV cure field. We previously initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following ... ...

Abstract	The discovery of biomarkers that predict viral rebound after discontinuation of antiretroviral therapy (ART) would significantly contribute to the HIV cure field. We previously initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection. After 6 months, we discontinued ART and observed viral rebound in 9 of 20 animals, which provided an opportunity to define peripheral biomarkers on ART that predicted viral rebound following ART discontinuation. We show that interleukin-1 (IL-1), IL-6_JAK_STAT3, IL-10, transforming growth factor β (TGF-β), IL-22, and IL-23 signaling and activation of monocyte, macrophage, and antigen processing and presentation pathways during ART suppression correlated with viral rebound. These signatures were validated in a second cohort of macaques. Our data suggest that low levels of antigen and proinflammatory signaling during ART suppression correlate with the presence of a rebound-competent viral reservoir. Interventions that modulate these peripheral biomarkers may be promising candidates to evaluate as potential HIV-1 cure strategies.
MeSH term(s)	Animals ; Simian Acquired Immunodeficiency Syndrome/drug therapy ; Simian Immunodeficiency Virus/physiology ; Macaca mulatta ; Anti-Retroviral Agents/therapeutic use ; Anti-Retroviral Agents/pharmacology ; Virus Replication ; HIV Infections/drug therapy ; Biomarkers
Chemical Substances	Anti-Retroviral Agents ; Biomarkers
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101122
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination.

Aid, Malika / Stephenson, Kathryn E / Collier, Ai-Ris Y / Nkolola, Joseph P / Michael, James V / McKenzie, Steven E / Barouch, Dan H

Nature communications

2023 Volume 14, Issue 1, Page(s) 6703

Abstract: Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been ...

Abstract	Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15-19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk.
MeSH term(s)	Humans ; Ad26COVS1 ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Proteomics ; Syndrome ; Thrombocytopenia/etiology ; Thrombosis/etiology ; Vaccination/adverse effects
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; BNT162 Vaccine ; COVID-19 Vaccines
Language	English
Publishing date	2023-10-23
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-42559-x
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Article ; Online: Attenuated

Vidal, Samuel J / Sellers, Daniel / Yu, Jingyou / Wakabayashi, Shoko / Sixsmith, Jaimie / Aid, Malika / Barrett, Julia / Stevens, Sage F / Liu, Xiaowen / Li, Wenjun / Plumlee, Courtney R / Urdahl, Kevin B / Martinot, Amanda J / Barouch, Dan H

iScience

2023 Volume 26, Issue 6, Page(s) 106963

Abstract: Bacillus Calmette-Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we show ... ...

Abstract	Bacillus Calmette-Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we show that the protective efficacy of a live attenuated
Language	English
Publishing date	2023-05-28
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106963
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Article ; Online: Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.

He, Xuan / Aid, Malika / Ventura, John D / Borducchi, Erica / Lifton, Michelle / Liu, Jinyan / Barouch, Dan H

Journal of virology

2022 Volume 96, Issue 17, Page(s) e0080822

Abstract: The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the ... ...

Abstract	The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16, a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies.
MeSH term(s)	Animals ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; Caspase 1/metabolism ; Cytokines ; Lymphoid Tissue/immunology ; Lymphoid Tissue/pathology ; Macaca mulatta/immunology ; Macaca mulatta/virology ; Pyroptosis ; Simian Acquired Immunodeficiency Syndrome/immunology ; Simian Acquired Immunodeficiency Syndrome/pathology ; Simian Acquired Immunodeficiency Syndrome/virology ; Simian Immunodeficiency Virus/immunology ; Simian Immunodeficiency Virus/pathogenicity
Chemical Substances	Cytokines ; Caspase 1 (EC 3.4.22.36)
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.00808-22
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Delineation and Modulation of the Natural Killer Cell Transcriptome in Rhesus Macaques During ZIKV and SIV Infections.

Aid, Malika / Ram, Daniel R / Bosinger, Steven E / Barouch, Dan H / Reeves, R Keith

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 194

Abstract: Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain ... ...

Abstract	Natural killer (NK) cells are crucial regulators of antiviral and anti-tumor immune responses. Although in humans some NK cell transcriptional programs are relatively well-established, NK cell transcriptional networks in non-human primates (NHP) remain poorly delineated. Here we performed RNA-Seq experiments using purified NK cells from experimentally naïve rhesus macaques, providing the first transcriptional characterization of pure NK cells in any NHP species. This novel NK cell transcriptomic signature (NK RMtsig) overlaps with published human NK signatures, allowing us to identify new key signaling and transcription factor networks underlying NK cell function. Finally, we show that applying NK RMtsig to an unrelated rhesus macaque cohort infected with SIVmac251 or ZIKV can sensitively detect NK cell repertoire perturbations, thus confirming applicability of this approach. In sum, we propose this NHP NK cell signature will serve as a useful resource for future studies involving infection, disease or treatment modalities in NHP.
MeSH term(s)	Animals ; Killer Cells, Natural ; Macaca mulatta ; Transcriptome ; Zika Virus ; Zika Virus Infection
Language	English
Publishing date	2020-04-29
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00194
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Article ; Online: Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination

Malika Aid / Kathryn E. Stephenson / Ai-ris Y. Collier / Joseph P. Nkolola / James V. Michael / Steven E. McKenzie / Dan H. Barouch

Nature Communications, Vol 14, Iss 1, Pp 1-

2023 Volume 10

Abstract: Abstract Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS ...

Abstract	Abstract Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15–19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk.
Keywords	Science ; Q
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ad26.COV2.S prevents upregulation of SARS-CoV-2 induced pathways of inflammation and thrombosis in hamsters and rhesus macaques.

Aid, Malika / Vidal, Samuel J / Piedra-Mora, Cesar / Ducat, Sarah / Chan, Chi N / Bondoc, Stephen / Colarusso, Alessandro / Starke, Carly E / Nekorchuk, Michael / Busman-Sahay, Kathleen / Estes, Jacob D / Martinot, Amanda J / Barouch, Dan H

PLoS pathogens

2022 Volume 18, Issue 4, Page(s) e1009990

Abstract: Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 WA1/2020 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I ... ...

Abstract	Syrian golden hamsters exhibit features of severe disease after SARS-CoV-2 WA1/2020 challenge and are therefore useful models of COVID-19 pathogenesis and prevention with vaccines. Recent studies have shown that SARS-CoV-2 infection stimulates type I interferon, myeloid, and inflammatory signatures similar to human disease and that weight loss can be prevented with vaccines. However, the impact of vaccination on transcriptional programs associated with COVID-19 pathogenesis and protective adaptive immune responses is unknown. Here we show that SARS-CoV-2 WA1/2020 challenge in hamsters stimulates myeloid and inflammatory programs as well as signatures of complement and thrombosis associated with human COVID-19. Notably, immunization with Ad26.COV2.S, an adenovirus serotype 26 vector (Ad26)-based vaccine expressing a stabilized SARS-CoV-2 spike protein, prevents the upregulation of these pathways, such that the mRNA expression profiles of vaccinated hamsters are comparable to uninfected animals. Using proteomics profiling, we validated these findings in rhesus macaques challenged with SARS-CoV-2 WA1/2020 or SARS-CoV-2 B.1.351. Finally, we show that Ad26.COV2.S vaccination induces T and B cell signatures that correlate with binding and neutralizing antibody responses weeks following vaccination. These data provide insights into the molecular mechanisms of Ad26.COV2.S protection against severe COVID-19 in animal models.
MeSH term(s)	Ad26COVS1 ; Animals ; Antibodies, Neutralizing ; COVID-19 ; COVID-19 Vaccines ; Cricetinae ; Humans ; Inflammation ; Macaca mulatta ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Thrombosis ; Up-Regulation
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; Antibodies, Neutralizing ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1009990
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Article ; Online: Attenuated Mycobacterium tuberculosis vaccine protection in a low-dose murine challenge model

Samuel J. Vidal / Daniel Sellers / Jingyou Yu / Shoko Wakabayashi / Jaimie Sixsmith / Malika Aid / Julia Barrett / Sage F. Stevens / Xiaowen Liu / Wenjun Li / Courtney R. Plumlee / Kevin B. Urdahl / Amanda J. Martinot / Dan H. Barouch

iScience, Vol 26, Iss 6, Pp 106963- (2023)

2023

Abstract: Summary: Bacillus Calmette–Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we ...

Abstract	Summary: Bacillus Calmette–Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we show that the protective efficacy of a live attenuated Mycobacterium tuberculosis (Mtb) vaccine ΔLprG markedly exceeds that of BCG in a low-dose murine aerosol challenge model. BCG reduced bacterial loads but did not prevent establishment or dissemination of infection in this model. In contrast, ΔLprG prevented detectable infection in 61% of mice and resulted in anatomic containment of 100% breakthrough infections to a single lung. Protection was partially abrogated in a repeated low-dose challenge model, which showed serum IL-17A, IL-6, CXCL2, CCL2, IFN-γ, and CXCL1 as correlates of protection. These data demonstrate that ΔLprG provides increased protection compared to BCG, including reduced detectable infection and anatomic containment, in a low-dose murine challenge model.
Keywords	Immunology ; Medical microbiology ; Science ; Q
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mpox infection protects against re-challenge in rhesus macaques.

Aid, Malika / Sciacca, Michaela / McMahan, Katherine / Hope, David / Liu, Jinyan / Jacob-Dolan, Catherine / Powers, Olivia / Barrett, Julia / Wu, Cindy / Mutoni, Audrey / Murdza, Tetyana / Richter, Hannah / Velasco, Jason / Teow, Elyse / Boursiquot, Mona / Cook, Anthony / Orekov, Tatyana / Hamilton, Melissa / Pessaint, Laurent /

Ryan, Alaina / Hayes, Tammy / Martinot, Amanda J / Seaman, Michael S / Lewis, Mark G / Andersen, Hanne / Barouch, Dan H

Cell

2023 Volume 186, Issue 21, Page(s) 4652–4661.e13

Abstract: The mpox outbreak of 2022-2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all ... ...

Abstract	The mpox outbreak of 2022-2023 involved rapid global spread in men who have sex with men. We infected 18 rhesus macaques with mpox by the intravenous, intradermal, and intrarectal routes and observed robust antibody and T cell responses following all three routes of infection. Numerous skin lesions and high plasma viral loads were observed following intravenous and intradermal infection. Skin lesions peaked on day 10 and resolved by day 28 following infection. On day 28, we re-challenged all convalescent and 3 naive animals with mpox. All convalescent animals were protected against re-challenge. Transcriptomic studies showed upregulation of innate and inflammatory responses and downregulation of collagen formation and extracellular matrix organization following challenge, as well as rapid activation of T cell and plasma cell responses following re-challenge. These data suggest key mechanistic insights into mpox pathogenesis and immunity. This macaque model should prove useful for evaluating mpox vaccines and therapeutics.
MeSH term(s)	Animals ; Humans ; Male ; Homosexuality, Male ; Macaca mulatta ; Mpox (monkeypox)/immunology ; Sexual and Gender Minorities ; Monkeypox virus/physiology
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.08.023
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Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

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Article ; Online: Plasma Proteomics of COVID-19-Associated Cardiovascular Complications: Implications for Pathophysiology and Therapeutics.

JACC. Basic to translational science

2022 Volume 7, Issue 5, Page(s) 425–441

Abstract: To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological ... ...

Abstract	To gain insights into the mechanisms driving cardiovascular complications in COVID-19, we performed a case-control plasma proteomics study in COVID-19 patients. Our results identify the senescence-associated secretory phenotype, a marker of biological aging, as the dominant process associated with disease severity and cardiac involvement. FSTL3, an indicator of senescence-promoting Activin/TGFβ signaling, and ADAMTS13, the von Willebrand Factor-cleaving protease whose loss-of-function causes microvascular thrombosis, were among the proteins most strongly associated with myocardial stress and injury. Findings were validated in a larger COVID-19 patient cohort and the hamster COVID-19 model, providing new insights into the pathophysiology of COVID-19 cardiovascular complications with therapeutic implications.
Language	English
Publishing date	2022-05-04
Publishing country	United States
Document type	Journal Article
ISSN	2452-302X
ISSN (online)	2452-302X
DOI	10.1016/j.jacbts.2022.01.013
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