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Article ; Online: Cutaneous presentation of Candida krusei fungemia refractory to amphotericin B.

Toker, Michelle / Kirkpatrick, Carson / Srivastava, Pooja / Amin, Bijal / Wu, Benedict

2023 , Page(s) e30366

Language	English
Publishing date	2023-04-19
Publishing country	United States
Document type	Letter
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.30366
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Article: Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.

Butler-Laporte, Guillaume / Auckland, Kathryn / Noor, Zannatun / Kabir, Mamun / Alam, Masud / Carstensen, Tommy / Wojcik, Genevieve L / Chong, Amanda Y / Pomilla, Cristina / Noble, Janelle A / McDevitt, Shana L / Smits, Gaby / Wareing, Susan / van der Klis, Fiona Rm / Jeffery, Katie / Kirkpatrick, Beth D / Sirima, Sodiomon / Madhi, Shabir / Elliott, Alison /

Richards, J Brent / Hill, Adrian Vs / Duggal, Priya / Sandhu, Manjinder S / Haque, Rashidul / Petri, William A / Mentzer, Alexander J

medRxiv : the preprint server for health sciences

2023

Abstract: Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening ...

Abstract	Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens. Using an HLA imputation panel with 9,448 south Asian individuals
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.06.26.23291885
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Article ; Online: Low protease activity in B cell follicles promotes retention of intact antigens after immunization.

Aung, Aereas / Cui, Ang / Maiorino, Laura / Amini, Ava P / Gregory, Justin R / Bukenya, Maurice / Zhang, Yiming / Lee, Heya / Cottrell, Christopher A / Morgan, Duncan M / Silva, Murillo / Suh, Heikyung / Kirkpatrick, Jesse D / Amlashi, Parastoo / Remba, Tanaka / Froehle, Leah M / Xiao, Shuhao / Abraham, Wuhbet / Adams, Josetta /

Love, J Christopher / Huyett, Phillip / Kwon, Douglas S / Hacohen, Nir / Schief, William R / Bhatia, Sangeeta N / Irvine, Darrell J

Science (New York, N.Y.)

2023 Volume 379, Issue 6630, Page(s) eabn8934

Abstract: The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that ...

Abstract	The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that antigens were rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions, whereas low protease activity and antigen degradation rates were detected in the vicinity of follicular dendritic cells (FDCs). Correlated with these findings, immunization regimens designed to target antigen to FDCs led to germinal centers dominantly targeting intact antigen, whereas traditional immunizations led to much weaker responses that equally targeted the intact immunogen and antigen breakdown products. Thus, spatially compartmentalized antigen proteolysis affects humoral immunity and can be exploited.
MeSH term(s)	Animals ; Humans ; Mice ; Antigens/immunology ; B-Lymphocytes/enzymology ; Endopeptidases/metabolism ; Germinal Center/enzymology ; Immunization ; Lymph Nodes/enzymology ; Proteolysis ; Vaccination
Chemical Substances	Antigens ; Endopeptidases (EC 3.4.-)
Language	English
Publishing date	2023-01-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abn8934
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Article ; Online: Immunity induced by vaccination with recombinant influenza B virus neuraminidase protein breaks viral transmission chains in guinea pigs in an exposure intensity-dependent manner.

McMahon, Meagan / Tan, Jessica / O'Dell, George / Kirkpatrick Roubidoux, Ericka / Strohmeier, Shirin / Krammer, Florian

Journal of virology

2023 Volume 97, Issue 10, Page(s) e0105723

Abstract: Importance: Vaccines that can slow respiratory virus transmission in the population are urgently needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Here, we describe how a recombinant neuraminidase-based ... ...

Abstract	Importance: Vaccines that can slow respiratory virus transmission in the population are urgently needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Here, we describe how a recombinant neuraminidase-based influenza virus vaccine reduces transmission in vaccinated guinea pigs in an exposure intensity-based manner.
MeSH term(s)	Animals ; Guinea Pigs ; Antibodies, Viral ; Influenza B virus ; Influenza Vaccines/immunology ; Neuraminidase/immunology ; Orthomyxoviridae Infections/prevention & control ; Recombinant Proteins ; Vaccination
Chemical Substances	Antibodies, Viral ; Influenza Vaccines ; Neuraminidase (EC 3.2.1.18) ; Recombinant Proteins
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01057-23
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Book ; Online: Neural Representation Learning for Scribal Hands of Linear B

Srivatsan, Nikita / Vega, Jason / Skelton, Christina / Berg-Kirkpatrick, Taylor

2021

Abstract: ... scribal hand analysis of the Linear B writing system. While prior work has demonstrated the usefulness ... to a given image. Among the key contributions of this work we (1) present a new dataset of Linear B glyphs ... of strategies such as phylogenetic systematics in tracing Linear B's history, these approaches have relied ...

Abstract	In this work, we present an investigation into the use of neural feature extraction in performing scribal hand analysis of the Linear B writing system. While prior work has demonstrated the usefulness of strategies such as phylogenetic systematics in tracing Linear B's history, these approaches have relied on manually extracted features which can be very time consuming to define by hand. Instead we propose learning features using a fully unsupervised neural network that does not require any human annotation. Specifically our model assigns each glyph written by the same scribal hand a shared vector embedding to represent that author's stylistic patterns, and each glyph representing the same syllabic sign a shared vector embedding to represent the identifying shape of that character. Thus the properties of each image in our dataset are represented as the combination of a scribe embedding and a sign embedding. We train this model using both a reconstructive loss governed by a decoder that seeks to reproduce glyphs from their corresponding embeddings, and a discriminative loss which measures the model's ability to predict whether or not an embedding corresponds to a given image. Among the key contributions of this work we (1) present a new dataset of Linear B glyphs, annotated by scribal hand and sign type, (2) propose a neural model for disentangling properties of scribal hands from glyph shape, and (3) quantitatively evaluate the learned embeddings on findplace prediction and similarity to manually extracted features, showing improvements over simpler baseline methods. Comment: ICDAR 2021 Workshop on Computational Paleography (1st edition)
Keywords	Computer Science - Computer Vision and Pattern Recognition ; Computer Science - Machine Learning
Subject code	006
Publishing date	2021-07-14
Publishing country	us
Document type	Book ; Online
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Article ; Online: Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model.

Nivarthi, Usha K / Tu, Huy A / Delacruz, Matthew J / Swanstrom, Jesica / Patel, Bhumi / Durbin, Anna P / Whitehead, Stephen S / Pierce, Kristen K / Kirkpatrick, Beth D / Baric, Ralph S / Nguyen, Ngan / Emerling, Daniel E / de Silva, Aravinda M / Diehl, Sean A

EBioMedicine

2019 Volume 41, Page(s) 465–478

Abstract: ... plasmablasts. At convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible ... relationships between antibodies produced by these B cell compartments are poorly understood.: Methods ... acute and convalescent B-cell responses.: Findings: The level of DENV2 replication was correlated ...

Abstract	Background: Acute viral infections induce a rapid and transient increase in antibody-secreting plasmablasts. At convalescence, memory B cells (MBC) and long-lived plasma cells (LLPC) are responsible for long-term humoral immunity. Following an acute viral infection, the specific properties and relationships between antibodies produced by these B cell compartments are poorly understood. Methods: We utilized a controlled human challenge model of primary dengue virus serotype 2 (DENV2) infection to study acute and convalescent B-cell responses. Findings: The level of DENV2 replication was correlated with the magnitude of the plasmablast response. Functional analysis of plasmablast-derived monoclonal antibodies showed that the DENV2-specific response was dominated by cells producing DENV2 serotype-specific antibodies. DENV2-neutralizing antibodies targeted quaternary structure epitopes centered on domain III of the viral envelope protein (EDIII). Functional analysis of MBC and serum antibodies from the same subjects six months post-challenge revealed maintenance of the serotype-specific response in both compartments. The serum response mainly targeted DENV2 serotype-specific epitopes on EDIII. Interpretation: Our data suggest overall functional alignment of DENV2-specific responses from the plasmablast, through the MBC and LLPC compartments following primary DENV2 inflection. These results provide enhanced resolution of the temporal and specificity of the B cell compartment in viral infection and serve as framework for evaluation of B cell responses in challenge models. Funding: This study was supported by the Bill and Melinda Gates Foundation and the National Institutes of Health.
MeSH term(s)	Acute Disease ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; B-Lymphocytes/cytology ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Dengue/diagnosis ; Dengue/virology ; Dengue Virus/genetics ; Dengue Virus/isolation & purification ; Epitope Mapping ; Epitopes/immunology ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/virology ; Longitudinal Studies ; Plasma Cells/cytology ; Plasma Cells/metabolism ; Serogroup ; Viral Envelope Proteins/immunology
Chemical Substances	Antibodies, Neutralizing ; Epitopes ; Viral Envelope Proteins
Language	English
Publishing date	2019-03-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2019.02.060
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Article ; Online: Development of Influenza B Universal Vaccine Candidates Using the "Mosaic" Hemagglutinin Approach.

Sun, Weina / Kirkpatrick, Ericka / Ermler, Megan / Nachbagauer, Raffael / Broecker, Felix / Krammer, Florian / Palese, Peter

Journal of virology

2019 Volume 93, Issue 12

Abstract: Influenza B viruses cause seasonal epidemics and are a considerable burden to public health ... In this study, we report a novel universal influenza B virus vaccination strategy based on "mosaic ... hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B ...

Abstract	Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. However, protection by current seasonal vaccines is suboptimal due to the antigenic changes of the circulating strains. In this study, we report a novel universal influenza B virus vaccination strategy based on "mosaic" hemagglutinins. We generated mosaic B hemagglutinins by replacing the major antigenic sites of the type B hemagglutinin with corresponding sequences from exotic influenza A hemagglutinins and expressed them as soluble trimeric proteins. Sequential vaccination with recombinant mosaic B hemagglutinin proteins conferred cross-protection against both homologous and heterologous influenza B virus strains in the mouse model. Of note, we rescued recombinant influenza B viruses expressing mosaic B hemagglutinins, which could serve as the basis for a universal influenza B virus vaccine.
MeSH term(s)	Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Cross Protection/immunology ; Cross Reactions/immunology ; Dogs ; Epitopes/immunology ; Female ; HEK293 Cells ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Hemagglutinins/immunology ; Humans ; Immunization, Passive ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H5N1 Subtype/immunology ; Influenza B virus/immunology ; Influenza Vaccines/therapeutic use ; Influenza, Human/immunology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/virology ; Vaccination/methods
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Influenza Vaccines
Language	English
Publishing date	2019-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.00333-19
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Article: Immunity induced by vaccination with recombinant influenza B virus neuraminidase protein breaks viral transmission chains in guinea pigs in an exposure intensity-dependent manner.

McMahon, Meagan / Tan, Jessica / O'Dell, George / Roubidoux, Ericka Kirkpatrick / Strohmeier, Shirin / Krammer, Florian

bioRxiv : the preprint server for biology

2022

Abstract: ... transmission of influenza B viruses in the guinea pig model. We tested four different scenarios ...

Abstract	Mucosal vaccines and vaccines that block pathogen transmission are under-appreciated in vaccine development. However, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that blocking viral transmission is an important attribute of efficient vaccines. Here, we investigated if recombinant influenza virus neuraminidase (NA) vaccines delivered at a mucosal site could protect from onward transmission of influenza B viruses in the guinea pig model. We tested four different scenarios in which sequential transmission was investigated in chains of four guinea pigs. The variables tested included a low and a high viral inoculum (10
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.10.19.512980
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Article ; Online: Characterization of Novel Cross-Reactive Influenza B Virus Hemagglutinin Head Specific Antibodies That Lack Hemagglutination Inhibition Activity.

Kirkpatrick, Ericka / Henry, Carole / McMahon, Meagan / Jiang, Kaijun / Strohmeier, Shirin / van Bakel, Harm / Wilson, Patrick C / Krammer, Florian

Journal of virology

2020 Volume 94, Issue 23

Abstract: ... four influenza B virus hemagglutinin (HA) head specific, hemagglutination inhibition-inactive ... monoclonal antibodies (MAbs) from elderly individuals. We found that they were broadly reactive within the B/Victoria/2 ... 1987-like lineage, and two were highly cross-reactive with B/Yamagata/16/1988-like lineage viruses ...

Abstract	Humoral immune responses to influenza virus vaccines in elderly individuals are poorly adapted toward new antigenically drifted influenza virus strains. Instead, older individuals respond in an original antigenic sin fashion and produce much more cross-reactive but less potent antibodies. Here, we investigated four influenza B virus hemagglutinin (HA) head specific, hemagglutination inhibition-inactive monoclonal antibodies (MAbs) from elderly individuals. We found that they were broadly reactive within the B/Victoria/2/1987-like lineage, and two were highly cross-reactive with B/Yamagata/16/1988-like lineage viruses. The MAbs were found to be neutralizing, to utilize Fc effector functions, and to be protective against lethal viral challenge in a mouse model. In order to identify residues on the influenza B virus hemagglutinin interacting with the MAbs, we generated escape mutant viruses. Interestingly, escape from these MAbs led to numerous HA mutations within the head domain, including in the defined antigenic sites. We observed that each individual escape mutant virus was able to avoid neutralization by its respective MAb along with other MAbs in the panel, although in many cases binding activity was maintained. Point mutant viruses indicated that K90 is critical for the neutralization of two MAbs, while escape from the other two MAbs required a combination of mutations in the hemagglutinin. Three of four escape mutant viruses had increased lethality in the DBA2/J mouse model. Our work indicates that these cross-reactive antibodies have the potential to cause antigenic drift in the viral population by driving mutations that increase virus fitness. However, binding activity and cross-neutralization were maintained by a majority of antibodies in the panel, suggesting that this drift may not lead to escape from antibody-mediated protection.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Cross Reactions ; Disease Models, Animal ; Female ; Hemagglutination ; Hemagglutination Inhibition Tests/methods ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Hemagglutinins/immunology ; Influenza B virus/genetics ; Influenza B virus/immunology ; Mice ; Mice, Inbred DBA ; Mutation ; Neutralization Tests ; Orthomyxoviridae Infections/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; Antigens, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins
Language	English
Publishing date	2020-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01185-20
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Article ; Online: Corrigendum to ''Longitudinal analysis of acute and convalescent B cell responses in a human primary dengue serotype 2 infection model'' [EBioMedicine 41 (2019) 465-478].

EBioMedicine

2020 Volume 54, Page(s) 102708

Language	English
Publishing date	2020-04-03
Publishing country	Netherlands
Document type	Journal Article ; Published Erratum
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2020.102708
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