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Article ; Online: Less BMI-1 is more for chronic infections.

Ripperger, Tyler J / Bhattacharya, Deepta

2021 Volume 23, Issue 1, Page(s) 6–8

MeSH term(s)	Body Mass Index ; Humans ; Obesity ; Persistent Infection ; Risk Factors
Language	English
Publishing date	2021-12-20
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01092-z
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Article ; Online: Transcriptional and Metabolic Control of Memory B Cells and Plasma Cells.

Ripperger, Tyler J / Bhattacharya, Deepta

Annual review of immunology

2021 Volume 39, Page(s) 345–368

Abstract: For many infections and almost all vaccines, neutralizing-antibody-mediated immunity is the primary basis and best functional correlate of immunological protection. Durable long-term humoral immunity is mediated by antibodies secreted by plasma cells ... ...

Abstract	For many infections and almost all vaccines, neutralizing-antibody-mediated immunity is the primary basis and best functional correlate of immunological protection. Durable long-term humoral immunity is mediated by antibodies secreted by plasma cells that preexist subsequent exposures and by memory B cells that rapidly respond to infections once they have occurred. In the midst of the current pandemic of coronavirus disease 2019, it is important to define our current understanding of the unique roles of memory B cells and plasma cells in immunity and the factors that control the formation and persistence of these cell types. This fundamental knowledge is the basis to interpret findings from natural infections and vaccines. Here, we review transcriptional and metabolic programs that promote and support B cell fates and functions, suggesting points at which these pathways do and do not intersect.
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Biomarkers ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Survival/genetics ; Cell Survival/immunology ; Energy Metabolism ; Gene Expression Regulation ; Germinal Center/immunology ; Germinal Center/metabolism ; Humans ; Immunologic Memory/genetics ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Plasma Cells/immunology ; Plasma Cells/metabolism ; Transcription, Genetic
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-02-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604953-9
ISSN	1545-3278 ; 0732-0582
ISSN (online)	1545-3278
ISSN	0732-0582
DOI	10.1146/annurev-immunol-093019-125603
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Article: Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy.

medRxiv : the preprint server for health sciences

2021

Abstract: Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic ... ...

Abstract	Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We compared immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=53) on active cytotoxic anti-cancer therapy to a control cohort (n=50) as an observational study. Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN
Language	English
Publishing date	2021-08-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2021.05.13.21257129
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Article ; Online: ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges.

Jash, Arijita / Zhou, You W / Gerardo, Diana K / Ripperger, Tyler J / Parikh, Bijal A / Piersma, Sytse / Jamwal, Deepa R / Kiela, Pawel R / Boon, Adrianus C M / Yokoyama, Wayne M / Hsieh, Chyi S / Bhattacharya, Deepta

Scientific reports

2019 Volume 9, Issue 1, Page(s) 15257

Abstract: ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed ... ...

Abstract	ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32
MeSH term(s)	Animals ; Antibodies, Viral/immunology ; Antibody Formation ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; Herpesviridae Infections/immunology ; Herpesviridae Infections/metabolism ; Immunologic Memory/immunology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Muromegalovirus/immunology ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
Chemical Substances	Antibodies, Viral ; Repressor Proteins ; Rog protein, mouse
Language	English
Publishing date	2019-10-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-51860-z
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Article ; Online: Affinity-Restricted Memory B Cells Dominate Recall Responses to Heterologous Flaviviruses.

Wong, Rachel / Belk, Julia A / Govero, Jennifer / Uhrlaub, Jennifer L / Reinartz, Dakota / Zhao, Haiyan / Errico, John M / D'Souza, Lucas / Ripperger, Tyler J / Nikolich-Zugich, Janko / Shlomchik, Mark J / Satpathy, Ansuman T / Fremont, Daved H / Diamond, Michael S / Bhattacharya, Deepta

Immunity

2020 Volume 53, Issue 5, Page(s) 1078–1094.e7

Abstract: Memory B cells (MBCs) can respond to heterologous antigens either by molding new specificities through secondary germinal centers (GCs) or by selecting preexisting clones without further affinity maturation. To distinguish these mechanisms in flavivirus ... ...

Abstract	Memory B cells (MBCs) can respond to heterologous antigens either by molding new specificities through secondary germinal centers (GCs) or by selecting preexisting clones without further affinity maturation. To distinguish these mechanisms in flavivirus infections and immunizations, we studied recall responses to envelope protein domain III (DIII). Conditional deletion of activation-induced cytidine deaminase (AID) between heterologous challenges of West Nile, Japanese encephalitis, Zika, and dengue viruses did not affect recall responses. DIII-specific MBCs were contained mostly within the plasma-cell-biased CD80
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Cross Reactions/immunology ; Disease Models, Animal ; Dose-Response Relationship, Immunologic ; Flavivirus/immunology ; Flavivirus Infections/immunology ; Flavivirus Infections/metabolism ; Flavivirus Infections/virology ; Host-Pathogen Interactions/immunology ; Immunization ; Immunologic Memory ; Mice ; Mice, Knockout ; Mice, Transgenic ; Plasma Cells/immunology ; Plasma Cells/metabolism ; Species Specificity
Language	English
Publishing date	2020-10-02
Publishing country	United States
Document type	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	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.09.001
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Immune responses to two and three doses of the BNT162b2 mRNA vaccine in adults with solid tumors.

Nature medicine

2021 Volume 27, Issue 11, Page(s) 2002–2011

Abstract: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA ... ...

Abstract	Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. In this study, we compared immune responses to the BNT162b2 mRNA Coronavirus Disease 2019 vaccine in patients with solid tumors (n = 53) who were on active cytotoxic anti-cancer therapy to a control cohort of participants without cancer (n = 50). Neutralizing antibodies were detected in 67% of patients with cancer after the first immunization, followed by a threefold increase in median titers after the second dose. Similar patterns were observed for spike protein-specific serum antibodies and T cells, but the magnitude of each of these responses was diminished relative to the control cohort. In most patients with cancer, we detected spike receptor-binding domain and other S1-specific memory B cell subsets as potential predictors of anamnestic responses to additional immunizations. We therefore initiated a phase 1 trial for 20 cancer cohort participants of a third vaccine dose of BNT162b2 ( NCT04936997 ); primary outcomes were immune responses, with a secondary outcome of safety. At 1 week after a third immunization, 16 participants demonstrated a median threefold increase in neutralizing antibody responses, but no improvement was observed in T cell responses. Adverse events were mild. These results suggest that a third dose of BNT162b2 is safe, improves humoral immunity against SARS-CoV-2 and could be immunologically beneficial for patients with cancer on active chemotherapy.
MeSH term(s)	Adult ; Aged ; Antibodies, Viral/blood ; Antibodies, Viral/metabolism ; Arizona ; BNT162 Vaccine/administration & dosage ; BNT162 Vaccine/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; Cohort Studies ; Dose-Response Relationship, Drug ; Female ; Humans ; Immunity, Humoral/drug effects ; Immunity, Humoral/physiology ; Male ; Middle Aged ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; RNA, Messenger/immunology ; RNA, Viral/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Young Adult
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; RNA, Viral ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; 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/s41591-021-01542-z
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: ZBTB32 restrains antibody responses to murine cytomegalovirus infections, but not other repetitive challenges

Arijita Jash / You W. Zhou / Diana K. Gerardo / Tyler J. Ripperger / Bijal A. Parikh / Sytse Piersma / Deepa R. Jamwal / Pawel R. Kiela / Adrianus C. M. Boon / Wayne M. Yokoyama / Chyi S. Hsieh / Deepta Bhattacharya

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 11

Abstract: Abstract ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we ... ...

Abstract	Abstract ZBTB32 is a transcription factor that is highly expressed by a subset of memory B cells and restrains the magnitude and duration of recall responses against hapten-protein conjugates. To define physiological contexts in which ZBTB32 acts, we assessed responses by Zbtb32 −/− mice or bone marrow chimeras against a panel of chronic and acute challenges. Mixed bone marrow chimeras were established in which all B cells were derived from either Zbtb32 −/− mice or control littermates. Chronic infection of Zbtb32 −/− chimeras with murine cytomegalovirus led to nearly 20-fold higher antigen-specific IgG2b levels relative to controls by week 9 post-infection, despite similar viral loads. In contrast, IgA responses and specificities in the intestine, where memory B cells are repeatedly stimulated by commensal bacteria, were similar between Zbtb32 −/− mice and control littermates. Finally, an infection and heterologous booster vaccination model revealed no role for ZBTB32 in restraining primary or recall antibody responses against influenza viruses. Thus, ZBTB32 does not limit recall responses to a number of physiological acute challenges, but does restrict antibody levels during chronic viral infections that periodically engage memory B cells. This restriction might selectively prevent recall responses against chronic infections from progressively overwhelming other antibody specificities.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy

medRxiv

Abstract: Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We evaluated immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=52) on active cytotoxic ... ...

Abstract	Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We evaluated immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=52) on active cytotoxic anti-cancer therapy. These responses were compared to a control cohort that also received the Pfizer/BioNTech vaccine (n=50). Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFN+ Spike-specific T cells. The magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD- and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to viral exposures or additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. These data suggest that a third immunization might elevate antibody responses in cancer patients to levels seen in healthy individuals after the second dose. Trials should be conducted to test these predictions.
Keywords	covid19
Language	English
Publishing date	2021-05-14
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2021.05.13.21257129
Database	COVID19

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Article: Detection, prevalence, and duration of humoral responses to SARS-CoV-2 under conditions of limited population exposure.

Ripperger, Tyler J / Uhrlaub, Jennifer L / Watanabe, Makiko / Wong, Rachel / Castaneda, Yvonne / Pizzato, Hannah A / Thompson, Mallory R / Bradshaw, Christine / Weinkauf, Craig C / Bime, Christian / Erickson, Heidi L / Knox, Kenneth / Bixby, Billie / Parthasarathy, Sairam / Chaudhary, Sachin / Natt, Bhupinder / Cristan, Elaine / Aini, Tammer El / Rischard, Franz /

Campion, Janet / Chopra, Madhav / Insel, Michael / Sam, Afshin / Knepler, James L / Capaldi, Andrew P / Spier, Catherine M / Dake, Michael D / Edwards, Taylor / Kaplan, Matthew E / Scott, Serena Jain / Hypes, Cameron / Mosier, Jarrod / Harris, David T / LaFleur, Bonnie J / Sprissler, Ryan / Nikolich-Žugich, Janko / Bhattacharya, Deepta

medRxiv : the preprint server for health sciences

2020

Abstract: We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus- ... ...

Abstract	We conducted an extensive serological study to quantify population-level exposure and define correlates of immunity against SARS-CoV-2. We found that relative to mild COVID-19 cases, individuals with severe disease exhibited elevated authentic virus-neutralizing titers and antibody levels against nucleocapsid (N) and the receptor binding domain (RBD) and the S2 region of spike protein. Unlike disease severity, age and sex played lesser roles in serological responses. All cases, including asymptomatic individuals, seroconverted by 2 weeks post-PCR confirmation. RBD- and S2-specific and neutralizing antibody titers remained elevated and stable for at least 2-3 months post-onset, whereas those against N were more variable with rapid declines in many samples. Testing of 5882 self-recruited members of the local community demonstrated that 1.24% of individuals showed antibody reactivity to RBD. However, 18% (13/73) of these putative seropositive samples failed to neutralize authentic SARS-CoV-2 virus. Each of the neutralizing, but only 1 of the non-neutralizing samples, also displayed potent reactivity to S2. Thus, inclusion of multiple independent assays markedly improved the accuracy of antibody tests in low seroprevalence communities and revealed differences in antibody kinetics depending on the viral antigen. In contrast to other reports, we conclude that immunity is durable for at least several months after SARS-CoV-2 infection.
Keywords	covid19
Language	English
Publishing date	2020-08-15
Publishing country	United States
Document type	Preprint
DOI	10.1101/2020.08.14.20174490
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Article ; Online: Orthogonal SARS-CoV-2 Serological Assays Enable Surveillance of Low-Prevalence Communities and Reveal Durable Humoral Immunity.

Immunity

2020 Volume 53, Issue 5, Page(s) 925–933.e4

Abstract: We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies ... ...

Abstract	We conducted a serological study to define correlates of immunity against SARS-CoV-2. Compared to those with mild coronavirus disease 2019 (COVID-19) cases, individuals with severe disease exhibited elevated virus-neutralizing titers and antibodies against the nucleocapsid (N) and the receptor binding domain (RBD) of the spike protein. Age and sex played lesser roles. All cases, including asymptomatic individuals, seroconverted by 2 weeks after PCR confirmation. Spike RBD and S2 and neutralizing antibodies remained detectable through 5-7 months after onset, whereas α-N titers diminished. Testing 5,882 members of the local community revealed only 1 sample with seroreactivity to both RBD and S2 that lacked neutralizing antibodies. This fidelity could not be achieved with either RBD or S2 alone. Thus, inclusion of multiple independent assays improved the accuracy of antibody tests in low-seroprevalence communities and revealed differences in antibody kinetics depending on the antigen. We conclude that neutralizing antibodies are stably produced for at least 5-7 months after SARS-CoV-2 infection.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/blood ; Antibodies, Viral/blood ; Arizona/epidemiology ; Betacoronavirus/immunology ; Betacoronavirus/isolation & purification ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques/methods ; Coronavirus Infections/blood ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Nucleocapsid Proteins ; Female ; Humans ; Immunity, Humoral ; Male ; Middle Aged ; Nucleocapsid Proteins/immunology ; Pandemics ; Phosphoproteins ; Pneumonia, Viral/blood ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Prevalence ; Protein Interaction Domains and Motifs ; SARS-CoV-2 ; Seroepidemiologic Studies ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/immunology ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Coronavirus Nucleocapsid Proteins ; Nucleocapsid Proteins ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2020.10.004
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