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Article ; Online: TLR Agonist Therapy of Metastatic Breast Cancer in Mice.

Klinman, Dennis M / Goguet, Emilie / Tross, Debra

Journal of immunotherapy (Hagerstown, Md. : 1997)

2023 Volume 46, Issue 5, Page(s) 170–177

Abstract: Toll-like receptor (TLR) 7/8 and 9 agonists stimulate an innate immune response that supports the development of tumor-specific immunity. Previous studies showed that either agonist individually could cure mice of small tumors and that when used in ... ...

Abstract	Toll-like receptor (TLR) 7/8 and 9 agonists stimulate an innate immune response that supports the development of tumor-specific immunity. Previous studies showed that either agonist individually could cure mice of small tumors and that when used in combination, they could prevent the progression of larger tumors (>300 mm 3 ). To examine whether these agents combined could control metastatic disease, syngeneic mice were challenged with the highly aggressive 66cl4 triple-negative breast tumor cell line. Treatment was not initiated until pulmonary metastases were established, as verified by bioluminescent imaging of luciferase-tagged tumor cells. Results show that combined therapy with TLR7/8 and TLR9 agonists delivered to both primary and metastatic tumor sites significantly reduced tumor burden and extended survival. The inclusion of cyclophosphamide and anti-PD-L1 resulted in optimal tumor control, characterized by a 5-fold increase in the average duration of survival.
MeSH term(s)	Mice ; Animals ; Toll-Like Receptor 9/agonists ; Immunotherapy ; Cell Line ; Adjuvants, Immunologic ; Lung Neoplasms/drug therapy
Chemical Substances	Toll-Like Receptor 9 ; Adjuvants, Immunologic
Language	English
Publishing date	2023-04-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000467
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Article ; Online: Bivalent Coronavirus Disease 2019 Vaccine Antibody Responses to Omicron Variants Suggest That Responses to Divergent Variants Would Be Improved With Matched Vaccine Antigens.

Wang, Wei / Goguet, Emilie / Paz, Stephanie / Vassell, Russell / Pollett, Simon / Mitre, Edward / Weiss, Carol D

The Journal of infectious diseases

2023 Volume 228, Issue 4, Page(s) 439–443

Abstract: We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron severe acute respiratory syndrome coronavirus 2 variants after a bivalent or ancestral coronavirus disease 2019 (COVID-19) messenger RNA booster vaccine or ... ...

Abstract	We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron severe acute respiratory syndrome coronavirus 2 variants after a bivalent or ancestral coronavirus disease 2019 (COVID-19) messenger RNA booster vaccine or postvaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately 2-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.
MeSH term(s)	Humans ; Antibody Formation ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2/genetics ; Antibodies, Neutralizing ; Antibodies, Viral
Chemical Substances	COVID-19 Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad111
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Article ; Online: Bivalent COVID-19 vaccine antibody responses to Omicron variants suggest that responses to divergent variants would be improved with matched vaccine antigens

Wang, Wei / Goguet, Emilie / Paz Padilla, Stephanie / Vassell, Russell / Pollett, Simon / Mitre, Edward / Weiss, Carol

medRxiv

Abstract: We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately ... ...

Abstract	We compared neutralizing antibody responses to BA.4/5, BQ.1.1, XBB, and XBB.1.5 Omicron SARS-CoV-2 variants after a bivalent or ancestral COVID-19 mRNA booster vaccine or post-vaccination infection. We found that the bivalent booster elicited moderately high antibody titers against BA.4/5 that were approximately two-fold higher against all Omicron variants than titers elicited by the monovalent booster. The bivalent booster elicited low but similar titers against both XBB and XBB.1.5 variants. These findings inform risk assessments for future COVID-19 vaccine recommendations and suggest that updated COVID-19 vaccines containing matched vaccine antigens to circulating divergent variants may be needed.
Keywords	covid19
Language	English
Publishing date	2023-02-24
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.02.22.23286320
Database	COVID19

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Article ; Online: PAM3 supports the generation of M2-like macrophages from lupus patient monocytes and improves disease outcome in murine lupus.

Horuluoglu, Begum / Bayik, Defne / Kayraklioglu, Neslihan / Goguet, Emilie / Kaplan, Mariana J / Klinman, Dennis M

Journal of autoimmunity

2019 Volume 99, Page(s) 24–32

Abstract: Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed ... ...

Abstract	Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages. This raised the possibility of PAM3 being used to normalize the M1:M2 ratio in SLE. Consistent with that possibility, monocytes from lupus patients differentiated into M2-like macrophages when treated with PAM3 in vitro. Furthermore, lupus-prone NZB x NZW F1 mice responded similarly to weekly PAM3 treatment. Normalization of the M2 macrophage frequency was associated with delayed disease progression, decreased autoantibody and inflammatory cytokine synthesis, reduced proteinuria and prolonged survival in NZB x NZW F1 mice. The ability of PAM3 to bias monocyte differentiation in favor of immunosuppressive macrophages may represent a novel approach to the therapy of SLE.
MeSH term(s)	Animals ; Cell Plasticity/drug effects ; Cell Plasticity/immunology ; Cytokines/metabolism ; Endocytosis/immunology ; Female ; Immunophenotyping ; Lipopeptides/pharmacology ; Lupus Erythematosus, Systemic/complications ; Lupus Erythematosus, Systemic/etiology ; Lupus Erythematosus, Systemic/metabolism ; Lupus Nephritis/etiology ; Lupus Nephritis/metabolism ; Lupus Nephritis/pathology ; Macrophage Activation/drug effects ; Macrophage Activation/immunology ; Macrophages/immunology ; Macrophages/metabolism ; Male ; Mice ; Monocytes/immunology ; Monocytes/metabolism ; Toll-Like Receptor 1/metabolism ; Toll-Like Receptor 2/metabolism
Chemical Substances	Cytokines ; Lipopeptides ; Pam(3)CSK(4) peptide ; Toll-Like Receptor 1 ; Toll-Like Receptor 2
Language	English
Publishing date	2019-01-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2019.01.004
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Article: Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera.

Wang, Wei / Bhushan, Gitanjali L / Paz, Stephanie / Stauft, Charles B / Selvaraj, Prabhu / Goguet, Emilie / Bishop-Lilly, Kimberly A / Subramanian, Rahul / Vassell, Russell / Lusvarghi, Sabrina / Cong, Yu / Agan, Brian / Richard, Stephanie A / Epsi, Nusrat J / Fries, Anthony / Fung, Christian K / Conte, Matthew A / Holbrook, Michael R / Wang, Tony T /

Burgess, Timothy H / Mitre, Edward / Pollett, Simon D / Katzelnick, Leah C / Weiss, Carol D

bioRxiv : the preprint server for biology

2024

Abstract: Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, ...

Abstract	Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
Language	English
Publishing date	2024-04-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.05.588359
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Article ; Online: Venom Atypical Extracellular Vesicles as Interspecies Vehicles of Virulence Factors Involved in Host Specificity: The Case of a

Wan, Bin / Goguet, Emilie / Ravallec, Marc / Pierre, Olivier / Lemauf, Séverine / Volkoff, Anne-Nathalie / Gatti, Jean-Luc / Poirié, Marylène

Frontiers in immunology

2019 Volume 10, Page(s) 1688

Abstract: Endoparasitoid wasps, which lay eggs inside the bodies of other insects, use various strategies to protect their offspring from the host immune response. The hymenopteran species of the ... ...

Abstract	Endoparasitoid wasps, which lay eggs inside the bodies of other insects, use various strategies to protect their offspring from the host immune response. The hymenopteran species of the genus
MeSH term(s)	Animals ; Drosophila melanogaster/immunology ; Extracellular Vesicles/immunology ; Hemocytes/immunology ; Host Specificity/immunology ; Host-Parasite Interactions ; Virulence Factors/immunology ; Wasp Venoms/immunology ; Wasps/immunology
Chemical Substances	Virulence Factors ; Wasp Venoms
Language	English
Publishing date	2019-07-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.01688
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Article ; Online: Antigenic cartography using hamster sera identifies SARS-CoV-2 JN.1 evasion seen in human XBB.1.5 booster sera

Wang, Wei / Bhushan, Gitanjali L. / Paz, Stephanie / Stauft, Charles B. / Selvaraj, Prabhu / Goguet, Emilie / Bishop-Lilly, Kimberly A. / Subramanian, Rahul / Vassell, Russell / Lusvarghi, Sabrina / Cong, Yu / Agan, Brian / Richard, Stephanie A. / Epsi, Nusrat J. / Fries, Anthony / Fung, Christian K. / Conte, Matthew A. / Holbrook, Michael R. / Wang, Tony T. /

Burgess, Timothy H. / Mitre, Edward / Pollett, Simon D. / Katzelnick, Leah C. / Weiss, Carol D.

bioRxiv

Abstract	Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with five to six-fold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a five-fold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.
Keywords	covid19
Language	English
Publishing date	2024-04-06
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.04.05.588359
Database	COVID19

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Article ; Online: Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability.

Graydon, Elizabeth K / Conner, Tonia L / Dunham, Kim / Olsen, Cara / Goguet, Emilie / Coggins, Si'Ana A / Rekedal, Marana / Samuels, Emily / Jackson-Thompson, Belinda / Moser, Matthew / Lindrose, Alyssa / Hollis-Perry, Monique / Wang, Gregory / Maiolatesi, Santina / Alcorta, Yolanda / Reyes, Anatalio / Wong, Mimi / Ramsey, Kathy / Davies, Julian /

Parmelee, Edward / Ortega, Orlando / Sanchez, Mimi / Moller, Sydney / Inglefield, Jon / Tribble, David / Burgess, Timothy / O'Connell, Robert / Malloy, Allison M W / Pollett, Simon / Broder, Christopher C / Laing, Eric D / Anderson, Stephen K / Mitre, Edward

Frontiers in immunology

2023 Volume 14, Page(s) 1225025

Abstract: Introduction: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline ... ...

Abstract	Introduction: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Methods: We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1 Results: Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1 Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.
MeSH term(s)	Animals ; Humans ; BNT162 Vaccine ; Leukocytes, Mononuclear ; Prospective Studies ; COVID-19/prevention & control ; SARS-CoV-2 ; Drug-Related Side Effects and Adverse Reactions ; Immunoglobulin G ; mRNA Vaccines
Chemical Substances	BNT162 Vaccine ; Immunoglobulin G
Language	English
Publishing date	2023-08-25
Publishing country	Switzerland
Document type	Observational Study ; Journal Article ; 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.2023.1225025
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Article ; Online: Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Goguet, Emilie / Olsen, Cara H / Meyer, William A / Ansari, Sara / Powers, John H / Conner, Tonia L / Coggins, Si'Ana A / Wang, Wei / Wang, Richard / Illinik, Luca / Sanchez Edwards, Margaret / Jackson-Thompson, Belinda M / Hollis-Perry, Monique / Wang, Gregory / Alcorta, Yolanda / Wong, Mimi A / Saunders, David / Mohammed, Roshila / Balogun, Bolatito /

Kobi, Priscilla / Kosh, Lakeesha / Bishop-Lilly, Kimberly / Cer, Regina Z / Arnold, Catherine E / Voegtly, Logan J / Fitzpatrick, Maren / Luquette, Andrea E / Malagon, Francisco / Ortega, Orlando / Parmelee, Edward / Davies, Julian / Lindrose, Alyssa R / Haines-Hull, Hannah / Moser, Matthew S / Samuels, Emily C / Rekedal, Marana S / Graydon, Elizabeth K / Malloy, Allison M W / Tribble, David R / Burgess, Timothy H / Campbell, Wesley / Robinson, Sara / Broder, Christopher C / O'Connell, Robert J / Weiss, Carol D / Pollett, Simon / Laing, Eric D / Mitre, Edward

Frontiers in immunology

2024 Volume 15, Page(s) 1287504

Abstract: Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States.: Methods: Serum and saliva samples from 176 vaccinated adults ... ...

Abstract	Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.
MeSH term(s)	Adult ; Humans ; COVID-19/prevention & control ; SARS-CoV-2 ; COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G
Chemical Substances	COVID-19 Vaccines ; Antibodies, Viral ; Immunoglobulin G
Language	English
Publishing date	2024-03-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1287504
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Comparative Cohort Study of Post-Acute Covid-19 Infection with a Nested, Randomized Controlled Trial of Ivabradine for Those With Postural Orthostatic Tachycardia Syndrome (The COVIVA Study)

medRxiv

Abstract: Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light- ... ...

Abstract	Background: Significant clinical similarities have been observed between the recently described Long-Haul COVID-19 (LHC) syndrome, Postural Orthostatic Tachycardia Syndrome (POTS) and Inappropriate Sinus Tachycardia (IST). Shared symptoms include light-headedness, palpitations, tremulousness, generalized weakness, blurred vision, chest pain, dyspnea, brain-fog, and fatigue. Ivabradine is a selective sinoatrial node blocker FDA-approved for management of tachycardia associated with stable angina and heart failure not fully managed by beta blockers. In our study we aim to identify risk factors underlying LHC, as well as the effectiveness of ivabradine in controlling heart rate dysregulations and POTS/IST related symptoms. Methods/Design: A detailed prospective phenotypic evaluation combined with multi-omic analysis of 200 LHC volunteers will be conducted to identify risk factors for autonomic dysfunction. A comparator group of 50 volunteers with documented COVID-19 but without LHC will be enrolled to better understand the risk factors for LHC and autonomic dysfunction. Those in the cohort who meet diagnostic criteria for POTS or IST will be included in a nested prospective, randomized, placebo-controlled trial to assess the impact of ivabradine on symptoms and heart rate, assessed non-invasively based on physiologic response and ambulatory electrocardiogram. Additionally, studies on catecholamine production, mast cell and basophil degranulation, inflammatory biomarkers, and indicators of metabolic dysfunction will be measured to potentially provide molecular classification and mechanistic insights. Discussion: Optimal therapies for dysautonomia, particularly associated with LHC, have yet to be defined. In the present study, ivabradine, one of numerous proposed interventions, will be systematically evaluated for therapeutic potential in LHC-associated POTS and IST. Additionally, this study will further refine the characteristics of the LHC-associated POTS/IST phenotype, genotype and transcriptional profile, including immunologic and multi-omic analysis of persistent immune activation and dysregulation. The study will also explore and identify potential endotheliopathy and abnormalities of the clotting cascade.
Keywords	covid19
Language	English
Publishing date	2023-04-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.04.25.23289110
Database	COVID19

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