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Article ; Online: The Emerging Role of MAIT Cell Responses in Viral Infections.

Sandberg, Johan K / Leeansyah, Edwin / Eller, Michael A / Shacklett, Barbara L / Paquin-Proulx, Dominic

Journal of immunology (Baltimore, Md. : 1950)

2023 Volume 211, Issue 4, Page(s) 511–517

Abstract: Mucosal-associated invariant T (MAIT) cells are unconventional T cells with innate-like antimicrobial responsiveness. MAIT cells are known for MR1 (MHC class I-related protein 1)-restricted recognition of microbial riboflavin metabolites giving them the ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are unconventional T cells with innate-like antimicrobial responsiveness. MAIT cells are known for MR1 (MHC class I-related protein 1)-restricted recognition of microbial riboflavin metabolites giving them the capacity to respond to a broad range of microbes. However, recent progress has shown that MAIT cells can also respond to several viral infections in humans and in mouse models, ranging from HIV-1 and hepatitis viruses to influenza virus and SARS-CoV-2, in a primarily cognate Ag-independent manner. Depending on the disease context MAIT cells can provide direct or indirect antiviral protection for the host and may help recruit other immune cells, but they may also in some circumstances amplify inflammation and aggravate immunopathology. Furthermore, chronic viral infections are associated with varying degrees of functional and numerical MAIT cell impairment, suggesting secondary consequences for host defense. In this review, we summarize recent progress and highlight outstanding questions regarding the emerging role of MAIT cells in antiviral immunity.
MeSH term(s)	Mice ; Animals ; Humans ; Mucosal-Associated Invariant T Cells ; COVID-19/metabolism ; SARS-CoV-2/metabolism ; Histocompatibility Antigens Class I/metabolism ; Antiviral Agents/metabolism ; Minor Histocompatibility Antigens/metabolism
Chemical Substances	Histocompatibility Antigens Class I ; Antiviral Agents ; Minor Histocompatibility Antigens
Language	English
Publishing date	2023-08-07
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300147
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Article ; Online: OMIP-098: A 26 parameter, 24 color flow cytometry panel for human memory NK cell phenotyping.

Creegan, Matthew / Degler, Justin / Paquin-Proulx, Dominic / Eller, Michael A / Machmach, Kawthar

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2023 Volume 103, Issue 12, Page(s) 941–946

MeSH term(s)	Humans ; Flow Cytometry ; Killer Cells, Natural ; Immunophenotyping
Language	English
Publishing date	2023-10-08
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.24802
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Zs.A 1688: 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)
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Article ; Online: Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production.

N'guessan, Kombo F / Machmach, Kawthar / Swafford, Isabella / Costanzo, Margaret C / Wieczorek, Lindsay / Kim, Dohoon / Akapirat, Siriwat / Polonis, Victoria R / Pitisuttithum, Punnee / Nitayaphan, Sorachai / Gurunathan, Sanjay / Sinangil, Faruk / Chariyalertsak, Suwat / Ake, Julie A / O'connell, Robert J / Vasan, Sandhya / Paquin-Proulx, Dominic

Frontiers in immunology

2024 Volume 15, Page(s) 1339727

Abstract: The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations ... ...

Abstract	The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.
MeSH term(s)	Adult ; Humans ; Antibody Formation ; HIV Infections/prevention & control ; HIV Seropositivity ; HIV-1 ; Immunity, Innate ; Immunoglobulin G ; Natural Killer T-Cells ; Vaccination ; Double-Blind Method
Chemical Substances	Immunoglobulin G
Language	English
Publishing date	2024-02-13
Publishing country	Switzerland
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1339727
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Article ; Online: High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection.

Graydon, Elizabeth K / Malloy, Allison M W / Machmach, Kawthar / Sun, Peifang / Paquin-Proulx, Dominic / Lizewski, Stephen / Lizewski, Rhonda / Weir, Dawn L / Goforth, Carl W / Anderson, Stephen K / Letizia, Andrew G / Mitre, Edward

Current research in immunology

2023 Volume 4, Page(s) 100064

Abstract: This study tested the hypothesis that high frequencies of natural killer (NK) cells are protective against symptomatic SARS-CoV-2 infection. Samples were utilized from the COVID-19 Health Action Response for Marines study, a prospective, observational ... ...

Abstract	This study tested the hypothesis that high frequencies of natural killer (NK) cells are protective against symptomatic SARS-CoV-2 infection. Samples were utilized from the COVID-19 Health Action Response for Marines study, a prospective, observational study of SARS-CoV-2 infection in which participants were enrolled prior to infection and then serially monitored for development of symptomatic or asymptomatic infection. Frequencies and phenotypes of NK cells (CD3
Language	English
Publishing date	2023-07-15
Publishing country	Netherlands
Document type	Journal Article
ISSN	2590-2555
ISSN (online)	2590-2555
DOI	10.1016/j.crimmu.2023.100064
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Article ; Online: Dynamics of IL-15/IL-15R-α expression in response to HSV-1 infection reveal a novel mode of viral immune evasion counteracted by iNKT cells.

Sobkowiak, Michał J / Paquin-Proulx, Dominic / Bosnjak, Lidija / Moll, Markus / Sällberg Chen, Margaret / Sandberg, Johan K

European journal of immunology

2021 Volume 52, Issue 3, Page(s) 462–471

Abstract: Herpes simplex virus type 1 (HSV-1) infects and persists in most of the human population. Interleukin-15 (IL-15) has an important role in the activation of cell-mediated immune responses and acts in complex with IL-15 receptor alpha (IL-15R-α) through ... ...

Abstract	Herpes simplex virus type 1 (HSV-1) infects and persists in most of the human population. Interleukin-15 (IL-15) has an important role in the activation of cell-mediated immune responses and acts in complex with IL-15 receptor alpha (IL-15R-α) through cell surface transpresentation. Here, we have examined the IL-15/IL-15R-α complex response dynamics during HSV-1 infection in human keratinocytes. Surface expression of the IL-15/IL-15R-α complex rapidly increased in response to HSV-1, reaching a peak around 12 h after infection. This response was dependent on detection of viral replication by TLR3, and enhancement of IL15 and IL15RA gene expression. Beyond the peak of expression, levels of IL-15 and IL-15R-α gradually declined, reaching a profound loss of surface expression beyond 24 h of infection. This involved the loss of IL15 and IL15RA transcription. Interestingly, invariant natural killer T (iNKT) cells inhibited the viral interference with IL-15/IL-15R-α complex expression in an IFNγ-dependent manner. These results indicate that rapid upregulation of the IL-15/IL-15R-α complex occurs in HSV-1 infected keratinocytes, and that this response is targeted by viral interference. Shutdown of the IL-15 axis represents a novel mode of HSV-1 immune evasion, which can be inhibited by the host iNKT cell response.
MeSH term(s)	Herpes Simplex ; Herpesvirus 1, Human ; Humans ; Immune Evasion ; Interleukin-15/metabolism ; Interleukin-15 Receptor alpha Subunit/metabolism ; Natural Killer T-Cells
Chemical Substances	Interleukin-15 ; Interleukin-15 Receptor alpha Subunit
Language	English
Publishing date	2021-12-26
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202149287
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Article ; Online: AP-1/c-Fos supports SIV and HIV-1 latency in CD4 T cells infected

Cobos Jiménez, Viviana / Geretz, Aviva / Tokarev, Andrey / Ehrenberg, Philip K / Deletsu, Selase / Machmach, Kawthar / Mudvari, Prakriti / Howard, J Natalie / Zelkoski, Amanda / Paquin-Proulx, Dominic / Del Prete, Gregory Q / Subra, Caroline / Boritz, Eli A / Bosque, Alberto / Thomas, Rasmi / Bolton, Diane L

iScience

2023 Volume 26, Issue 10, Page(s) 108015

Abstract: Persistent HIV-1 reservoirs of infected CD4 T cells are a major barrier to HIV-1 cure, although the mechanisms by which they are established and ... ...

Abstract	Persistent HIV-1 reservoirs of infected CD4 T cells are a major barrier to HIV-1 cure, although the mechanisms by which they are established and maintained
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108015
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Article ; Online: Humoral immune responses associated with control of SARS-CoV-2 breakthrough infections in a vaccinated US military population.

Gromowski, Gregory D / Cincotta, Camila Macedo / Mayer, Sandra / King, Jocelyn / Swafford, Isabella / McCracken, Michael K / Coleman, Dante / Enoch, Jennifer / Storme, Casey / Darden, Janice / Peel, Sheila / Epperson, Diane / McKee, Kelly / Currier, Jeffrey R / Okulicz, Jason / Paquin-Proulx, Dominic / Cowden, Jessica / Peachman, Kristina

EBioMedicine

2023 Volume 94, Page(s) 104683

Abstract: Background: COVID-19 vaccines have been critical for protection against severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but gaps remain in our understanding of the immune responses that contribute to ... ...

Abstract	Background: COVID-19 vaccines have been critical for protection against severe disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but gaps remain in our understanding of the immune responses that contribute to controlling subclinical and mild infections. Methods: Vaccinated, active-duty US military service members were enrolled in a non-interventional, minimal-risk, observational study starting in May, 2021. Clinical data, serum, and saliva samples were collected from study participants and were used to characterise the humoral immune responses to vaccination and to assess its impact on clinical and subclinical infections, as well as virologic outcomes of breakthrough infections (BTI) including viral load and infection duration. Findings: The majority of VIRAMP participants had received the Pfizer COVID-19 vaccine and by January, 2022, N = 149 had a BTI. The median BTI duration (PCR+ days) was 4 days and the interquartile range was 1-8 days. Participants that were nucleocapsid seropositive prior to their BTI had significantly higher levels of binding and functional antibodies to the spike protein, shorter median duration of infections, and lower median peak viral loads compared to seronegative participants. Furthermore, levels of neutralising antibody, ACE2 blocking activity, and spike-specific IgA measured prior to BTI also correlated with the duration of infection. Interpretation: We extended previous findings and demonstrate that a subset of vaccine-induced humoral immune responses, along with nucleocapsid serostatus are associated with control of SARS-CoV-2 breakthrough infections in the upper airways. Funding: This work was funded by the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) in collaboration with the Defense Health Agency (DHA) COVID-19 funding initiative for the VIRAMP study.
MeSH term(s)	Humans ; COVID-19 Vaccines ; COVID-19 ; SARS-CoV-2 ; Immunity, Humoral ; Military Personnel ; Breakthrough Infections ; Antibodies, Neutralizing ; Antibodies, Viral ; Vaccination
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-07-04
Publishing country	Netherlands
Document type	Observational Study ; Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104683
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Article ; Online: Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability.

Shubin, Zhanna / Stanfield-Oakley, Sherry / Puangkaew, Jiraporn / Pitisutthithum, Punnee / Nitayaphan, Sorachai / Gurunathan, Sanjay / Sinangil, Faruk / Chariyalertsak, Suwat / Phanuphak, Nittaya / Ake, Julie A / O'Connell, Robert J / Vasan, Sandhya / Akapirat, Siriwat / Eller, Michael A / Ferrari, Guido / Paquin-Proulx, Dominic

AIDS (London, England)

2023 Volume 37, Issue 10, Page(s) 1519–1524

Abstract: Objectives: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen ...

Abstract	Objectives: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. Design: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. Methods: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. Results: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24-26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. Conclusion: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.
MeSH term(s)	Adult ; Humans ; AIDS Vaccines ; Antibody Formation ; HIV Antibodies ; HIV Infections/prevention & control ; HIV-1 ; Immunoglobulin G ; Vaccination ; Double-Blind Method
Chemical Substances	AIDS Vaccines ; HIV Antibodies ; Immunoglobulin G
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003611
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Article ; Online: Impact of the expression system on the immune responses to self-assembling protein nanoparticles (SAPNs) displaying HIV-1 V1V2 loop.

Karch, Christopher P / Paquin-Proulx, Dominic / Eller, Michael A / Matyas, Gary R / Burkhard, Peter / Beck, Zoltan

Nanomedicine : nanotechnology, biology, and medicine

2020 Volume 29, Page(s) 102255

Abstract: The V1V2 loop of the Env protein is a major target for HIV-1 vaccine development because in multiple studies antibodies to this region correlated with protection. Although SAPNs expressed in E. coli elicited anti-V1V2 antibodies, the Env protein is ... ...

Abstract	The V1V2 loop of the Env protein is a major target for HIV-1 vaccine development because in multiple studies antibodies to this region correlated with protection. Although SAPNs expressed in E. coli elicited anti-V1V2 antibodies, the Env protein is heavily glycosylated. In this study the technology has been adapted for expression in mammalian cells. SAPNs containing a V1V2 loop from a B-subtype transmitter/founder virus were expressed in E. coli, ExpiCHO, and Expi293 cells. Independent of the expression host, particles were well-formed. All SAPNs raised high titers of V1V2-specific antibodies, however, SAPN
MeSH term(s)	Animals ; Antibodies, Monoclonal/genetics ; Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/drug effects ; Antibodies, Neutralizing/immunology ; Epitopes/drug effects ; Epitopes/immunology ; Escherichia coli/genetics ; Gene Products, env/genetics ; Gene Products, env/immunology ; HIV Infections/genetics ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; HIV-1/pathogenicity ; Humans ; Immunity/genetics ; Immunity/immunology ; Immunization ; Nanoparticles/chemistry
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Epitopes ; Gene Products, env
Language	English
Publishing date	2020-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2020.102255
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Article ; Online: Dicer-2 Regulates Resistance and Maintains Homeostasis against Zika Virus Infection in

Harsh, Sneh / Ozakman, Yaprak / Kitchen, Shannon M / Paquin-Proulx, Dominic / Nixon, Douglas F / Eleftherianos, Ioannis

Journal of immunology (Baltimore, Md. : 1950)

2018 Volume 201, Issue 10, Page(s) 3058–3072

Abstract: Zika virus (ZIKV) outbreaks pose a massive public health threat in several countries. We have developed an in vivo model to investigate the host-ZIKV interaction ... ...

Abstract	Zika virus (ZIKV) outbreaks pose a massive public health threat in several countries. We have developed an in vivo model to investigate the host-ZIKV interaction in
MeSH term(s)	Animals ; Disease Models, Animal ; Drosophila Proteins/immunology ; Drosophila melanogaster/immunology ; Drosophila melanogaster/virology ; Homeostasis/immunology ; Host-Pathogen Interactions/immunology ; RNA Helicases/immunology ; Ribonuclease III/immunology ; Zika Virus Infection/immunology
Chemical Substances	Drosophila Proteins ; DCR-2 protein, Drosophila (EC 2.7.7.-) ; Ribonuclease III (EC 3.1.26.3) ; RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2018-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1800597
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