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Article ; Online: Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species

Nicholas S. Rhoades / Isaac R. Cinco / Sara M. Hendrickson / Kamm Prongay / Andrew J. Haertel / Gilberto E. Flores / Mark K. Slifka / Ilhem Messaoudi

Communications Biology, Vol 7, Iss 1, Pp 1-

2024 Volume 14

Abstract: Abstract Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading ... ...

Abstract	Abstract Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species. Finally, we compared the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance of unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.
Keywords	Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Campylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques

Sara M. Hendrickson / Archana Thomas / Hans-Peter Raué / Kamm Prongay / Andrew J. Haertel / Nicholas S. Rhoades / Jacob F. Slifka / Lina Gao / Benjamin K. Quintel / Ian J. Amanna / Ilhem Messaoudi / Mark K. Slifka

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

2023 Volume 16

Abstract: Abstract Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we ... ...

Abstract	Abstract Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we examine naturally occurring Campylobacter-associated diarrhea among rhesus macaques as a model to determine if vaccination could reduce severe diarrheal disease and infant growth stunting. Compared to unvaccinated controls, there are no Campylobacter diarrhea-associated deaths observed among vaccinated infant macaques and all-cause diarrhea-associated infant mortality is decreased by 76% (P = 0.03). By 9 months of age, there is a 1.3 cm increase in dorsal length that equaled a significant 1.28 LAZ (Length-for-Age Z score) improvement in linear growth among vaccinated infants compared to their unvaccinated counterparts (P = 0.001). In this work, we show that Campylobacter vaccination not only reduces diarrheal disease but also potentially serves as an effective intervention that improves infant growth trajectories.
Keywords	Science ; Q
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine

Sara M. Hendrickson / Archana Thomas / Kamm Prongay / Andrew J. Haertel / Laura M. Garzel / Leanne Gill / Tasha Barr / Nicholas S. Rhoades / Rachel Reader / Mark Galan / Julie M. Carroll / Charles T. Roberts / Lina Gao / Ian J. Amanna / Ilhem Messaoudi / Mark K. Slifka

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 13

Abstract: Environmental enteric dysfunction (EED), a subclinical disorder of intestinal function, is associated with malnutrition, infant growth stunting and pathologies in the small intestine. Here the authors report that infant rhesus macaques that are naturally ...

Abstract	Environmental enteric dysfunction (EED), a subclinical disorder of intestinal function, is associated with malnutrition, infant growth stunting and pathologies in the small intestine. Here the authors report that infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting present with EED and growth faltering that associates with large intestine pathologies.
Keywords	Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plasma cell survival in the absence of B cell memory

Erika Hammarlund / Archana Thomas / Ian J. Amanna / Lindsay A. Holden / Ov D. Slayden / Byung Park / Lina Gao / Mark K. Slifka

Nature Communications, Vol 8, Iss 1, Pp 1-

2017 Volume 11

Abstract: The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B ... ...

Abstract	The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.
Keywords	Science ; Q
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plasma cell survival in the absence of B cell memory

Erika Hammarlund / Archana Thomas / Ian J. Amanna / Lindsay A. Holden / Ov D. Slayden / Byung Park / Lina Gao / Mark K. Slifka

Nature Communications, Vol 8, Iss 1, Pp 1-

2017 Volume 11

Abstract	The long-term maintenance of antibody-secreting plasma cells and the requirement for memory B cells are unclear. Here, the authors show that plasma cells and the antibodies secreted are long-lived and maintained over a decade in the absence of memory B cells in non-human primates.
Keywords	Science ; Q
Language	English
Publishing date	2017-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Retrospective Analysis of Monkeypox Infection

Melissa E. Dubois / Mark K. Slifka

Emerging Infectious Diseases, Vol 14, Iss 4, Pp 592-

2008 Volume 599

Abstract: Serologic cross-reactivity between orthopoxviruses is a substantial barrier to laboratory diagnosis of specific orthopoxvirus infections and epidemiologic characterization of disease outbreaks. Historically, time-consuming and labor-intensive strategies ... ...

Abstract	Serologic cross-reactivity between orthopoxviruses is a substantial barrier to laboratory diagnosis of specific orthopoxvirus infections and epidemiologic characterization of disease outbreaks. Historically, time-consuming and labor-intensive strategies such as cross-adsorbed neutralization assays, immunofluorescence assays, and hemagglutination-inhibition assays have been used to identify orthopoxvirus infections. We used cross-adsorption to develop a simple and quantitative postadsorption ELISA for distinguishing between monkeypox and vaccinia infections. Despite the difficulty of diagnosing clinically inapparent monkeypox in previously vaccinated persons, this technique exhibited 100% sensitivity and 100% specificity for identifying clinically overt monkeypox infection irrespective of vaccination history. We also describe a Western blot technique in which up to 3 diagnostic bands may be used to distinguish between vaccinia and monkeypox infection. The techniques described provide independent diagnostic tests suitable for retrospective analysis of monkeypox outbreaks.
Keywords	Monkeypox ; vaccinia ; differential diagnosis ; serologic diagnostics ; research ; United States ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2008-04-01T00:00:00Z
Publisher	Centers for Disease Control and Prevention
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lymphatic Vessels Balance Viral Dissemination and Immune Activation following Cutaneous Viral Infection

Christopher P. Loo / Nicholas A. Nelson / Ryan S. Lane / Jamie L. Booth / Sofia C. Loprinzi Hardin / Archana Thomas / Mark K. Slifka / Jeffrey C. Nolz / Amanda W. Lund

Cell Reports, Vol 20, Iss 13, Pp 3176-

2017 Volume 3187

Abstract: Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to ... ...

Abstract	Lymphatic vessels lie at the interface between peripheral sites of pathogen entry, adaptive immunity, and the systemic host. Though the paradigm is that their open structure allows for passive flow of infectious particles from peripheral tissues to lymphoid organs, virus applied to skin by scarification does not spread to draining lymph nodes. Using cutaneous infection by scarification, we analyzed the effect of viral infection on lymphatic transport and evaluated its role at the host-pathogen interface. We found that, in the absence of lymphatic vessels, canonical lymph-node-dependent immune induction was impaired, resulting in exacerbated pathology and compensatory, systemic priming. Furthermore, lymphatic vessels decouple fluid and cellular transport in an interferon-dependent manner, leading to viral sequestration while maintaining dendritic cell transport for immune induction. In conclusion, we found that lymphatic vessels balance immune activation and viral dissemination and act as an “innate-like” component of tissue host viral defense.
Keywords	lymphatic vessels ; cutaneous infection ; vaccinia virus ; type I interferons ; dissemination ; tissue microenvironment ; tissue immunity ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus.

Erika Hammarlund / Ian J Amanna / Melissa E Dubois / Alex Barron / Flora Engelmann / Ilhem Messaoudi / Mark K Slifka

PLoS ONE, Vol 7, Iss 9, p e

2012 Volume 41707

Abstract: Primary clinical isolates of yellow fever virus can be difficult to quantitate by standard in vitro methods because they may not form discernable plaques or induce a measurable cytopathic effect (CPE) on cell monolayers. In our hands, the Dakar strain of ...

Abstract	Primary clinical isolates of yellow fever virus can be difficult to quantitate by standard in vitro methods because they may not form discernable plaques or induce a measurable cytopathic effect (CPE) on cell monolayers. In our hands, the Dakar strain of yellow fever virus (YFV-Dakar) could not be measured by plaque assay (PA), focus-forming assay (FFA), or by measurement of CPE. For these reasons, we developed a YFV-specific monoclonal antibody (3A8.B6) and used it to optimize a highly sensitive flow cytometry-based tissue culture limiting dilution assay (TC-LDA) to measure levels of infectious virus. The TC-LDA was performed by incubating serial dilutions of virus in replicate wells of C6/36 cells and stained intracellularly for virus with MAb 3A8.B6. Using this approach, we could reproducibly quantitate YFV-Dakar in tissue culture supernatants as well as from the serum of viremic rhesus macaques experimentally infected with YFV-Dakar. Moreover, the TC-LDA approach was >10-fold more sensitive than standard plaque assay for quantitating typical plaque-forming strains of YFV including YFV-17D and YFV-FNV (French neurotropic vaccine). Together, these results indicate that the TC-LDA technique is effective for quantitating both plaque-forming and non-plaque-forming strains of yellow fever virus, and this methodology may be readily adapted for the study and quantitation of other non-plaque-forming viruses.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pathophysiologic and transcriptomic analyses of viscerotropic yellow fever in a rhesus macaque model.

Flora Engelmann / Laurence Josset / Thomas Girke / Byung Park / Alex Barron / Jesse Dewane / Erika Hammarlund / Anne Lewis / Michael K Axthelm / Mark K Slifka / Ilhem Messaoudi

PLoS Neglected Tropical Diseases, Vol 8, Iss 11, p e

2014 Volume 3295

Abstract: Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have ... ...

Abstract	Infection with yellow fever virus (YFV), an explosively replicating flavivirus, results in viral hemorrhagic disease characterized by cardiovascular shock and multi-organ failure. Unvaccinated populations experience 20 to 50% fatality. Few studies have examined the pathophysiological changes that occur in humans during YFV infection due to the sporadic nature and remote locations of outbreaks. Rhesus macaques are highly susceptible to YFV infection, providing a robust animal model to investigate host-pathogen interactions. In this study, we characterized disease progression as well as alterations in immune system homeostasis, cytokine production and gene expression in rhesus macaques infected with the virulent YFV strain DakH1279 (YFV-DakH1279). Following infection, YFV-DakH1279 replicated to high titers resulting in viscerotropic disease with ∼72% mortality. Data presented in this manuscript demonstrate for the first time that lethal YFV infection results in profound lymphopenia that precedes the hallmark changes in liver enzymes and that although tissue damage was noted in liver, kidneys, and lymphoid tissues, viral antigen was only detected in the liver. These observations suggest that additional tissue damage could be due to indirect effects of viral replication. Indeed, circulating levels of several cytokines peaked shortly before euthanasia. Our study also includes the first description of YFV-DakH1279-induced changes in gene expression within peripheral blood mononuclear cells 3 days post-infection prior to any clinical signs. These data show that infection with wild type YFV-DakH1279 or live-attenuated vaccine strain YFV-17D, resulted in 765 and 46 differentially expressed genes (DEGs), respectively. DEGs detected after YFV-17D infection were mostly associated with innate immunity, whereas YFV-DakH1279 infection resulted in dysregulation of genes associated with the development of immune response, ion metabolism, and apoptosis. Therefore, WT-YFV infection is associated with significant changes in gene ...
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	570
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine

Poore, Elizabeth A / Archana Thomas / Ariel M. Slifka / Benjamin K. Quintel / Dawn K. Slifka / Erika Hammarlund / Hans-Peter Raué / Ian J. Amanna / Justin M. Richner / Lawrence P. Johnson / Lindsay L. Torrey / Mark K. Slifka / Melissa E. Dubois / Michael S. Diamond

Vaccine. 2017 Jan. 05, v. 35, no. 2

2017

Abstract: West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United ... ...

Abstract	West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2–8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate.
Keywords	death ; humans ; immune response ; injection site ; Macaca mulatta ; manufacturing ; mice ; mortality ; neutralizing antibodies ; pathogens ; public health ; rats ; risk ; toxicology ; vaccination ; vaccines ; viremia ; virion ; West Nile virus ; United States
Language	English
Dates of publication	2017-0105
Size	p. 283-292.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2016.11.080
Database	NAL-Catalogue (AGRICOLA)

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