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Article: Novel Tools for Lassa Virus Surveillance in Peri-domestic Rodents.

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Lassa fever (LF) is a rodent-borne disease endemic to West Africa. In the absence of licensed therapeutics or vaccines, rodent exclusion from living spaces remains the primary method of preventing LF. Zoonotic surveillance of Lassa virus ( ... ...

Abstract	Background: Lassa fever (LF) is a rodent-borne disease endemic to West Africa. In the absence of licensed therapeutics or vaccines, rodent exclusion from living spaces remains the primary method of preventing LF. Zoonotic surveillance of Lassa virus (LASV), the etiologic agent of LF, can assess the burden of LASV in a region and guide public health measures against LF. Methods: In this study, we adapted commercially available LASV human diagnostics to assess the prevalence of LASV in peri-domestic rodents in Eastern Sierra Leone. Small mammal trapping was conducted in Kenema district, Sierra Leone between November 2018-July 2019. LASV antigen was detected using a commercially available LASV NP antigen rapid diagnostic test. LASV IgG antibodies against LASV nucleoprotein (NP) and glycoprotein (GP) were tested by adapting a commercially available semi-quantitative enzyme linked immunosorbent assay (ELISA) for detection of mouse-related and rat-related species IgG. Findings: Of the 373 tested specimens, 74 (20%) tested positive for LASV antigen. 40 (11%) specimens tested positive for LASV NP IgG, while an additional 12 (3%) specimens only tested positive for LASV GP IgG. Simultaneous antigen presence and IgG antibody presence was linked in Interpretation: The tools developed in this study can aid in the generation of valuable public health data for rapid field assessment of LASV burden during outbreak investigations and general LASV surveillance. Funding: Funding for this work was supported by the National Institute of Allergy and Infectious Diseases National Institute of Health, Department of Health and Human Services under the following grants: International Collaboration in Infectious Disease Research on Lassa fever and Ebola - ICIDR - U19 AI115589, Consortium for Viral Systems Biology - CViSB - 5U19AI135995, West African Emerging Infectious Disease Research Center - WARN-ID - U01AI151812, West African Center for Emerging Infectious Diseases: U01AI151801.
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.17.23287380
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Article ; Online: Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail.

Drouin, Arnaud C / Theberge, Marc W / Liu, Sharon Y / Smither, Allison R / Flaherty, Shelby M / Zeller, Mark / Geba, Gregory P / Reynaud, Peter / Rothwell, W Benjamin / Luk, Alfred P / Tian, Di / Boisen, Matthew L / Branco, Luis M / Andersen, Kristian G / Robinson, James E / Garry, Robert F / Fusco, Dahlene N

Viruses

2021 Volume 13, Issue 7

Abstract: A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course ...

Abstract	A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient's family. Current decisions to take revolve around patient's follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; B-Lymphocytes/immunology ; COVID-19/complications ; COVID-19/immunology ; COVID-19/therapy ; Humans ; Immunity, Humoral ; Lymphocyte Depletion ; Lymphoma, Follicular/drug therapy ; Lymphoma, Follicular/therapy ; Male ; Middle Aged ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; Viral Vaccines/administration & dosage ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Monoclonal ; Spike Glycoprotein, Coronavirus ; Viral Vaccines ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-06-23
Publishing country	Switzerland
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071202
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Article ; Online: Exposure modality influences viral kinetics but not respiratory outcome of COVID-19 in multiple nonhuman primate species.

PLoS pathogens

2022 Volume 18, Issue 7, Page(s) e1010618

Abstract: The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe ... ...

Abstract	The novel coronavirus SARS-CoV-2 emerged in late 2019, rapidly reached pandemic status, and has maintained global ubiquity through the emergence of variants of concern. Efforts to develop animal models have mostly fallen short of recapitulating severe disease, diminishing their utility for research focusing on severe disease pathogenesis and life-saving medical countermeasures. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species of nonhuman primates (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM). Species-specific cohorts were experimentally infected with SARS-CoV-2 by either direct mucosal (intratracheal + intranasal) instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated analogous viral loads in all compartments by either exposure route although the magnitude and duration of viral loading was marginally greater in AGMs than RMs. Clinical onset was nearly immediate (+1dpi) in the mucosal exposure cohort whereas clinical signs and cytokine responses in aerosol exposure animals began +7dpi. Pathologies conserved in both species and both exposure modalities include pulmonary myeloid cell influx, development of pleuritis, and extended lack of regenerative capacity in the pulmonary compartment. Demonstration of conserved pulmonary pathology regardless of species and exposure route expands our understanding of how SARS-CoV-2 infection may lead to ARDS and/or functional lung damage and demonstrates the near clinical response of the nonhuman primate model for anti-fibrotic therapeutic evaluation studies.
MeSH term(s)	Aerosols ; Animals ; COVID-19 ; Chlorocebus aethiops ; Disease Models, Animal ; Humans ; Lung/pathology ; Macaca mulatta ; SARS-CoV-2
Chemical Substances	Aerosols
Language	English
Publishing date	2022-07-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1010618
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Article: Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail

Drouin, Arnaud C. / Theberge, Marc W. / Liu, Sharon Y. / Smither, Allison R. / Flaherty, Shelby M. / Zeller, Mark / Geba, Gregory P. / Reynaud, Peter / Rothwell, W. Benjamin / Luk, Alfred P. / Tian, Di / Boisen, Matthew L. / Branco, Luis M. / Andersen, Kristian G. / Robinson, James E. / Garry, Robert F. / Fusco, Dahlene N.

Viruses. 2021 June 23, v. 13, no. 7

2021

Abstract	A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient’s family. Current decisions to take revolve around patient’s follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.
Keywords	B-lymphocytes ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; disease course ; drug therapy ; health care workers ; humoral immunity ; lymphoma ; males ; monoclonal antibodies ; patients ; pharmacology ; quarantine ; vaccination ; virology ; viruses
Language	English
Dates of publication	2021-0623
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13071202
Database	NAL-Catalogue (AGRICOLA)

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Article: Space-Time Trends in Lassa Fever in Sierra Leone by ELISA Serostatus, 2012–2019

Microorganisms. 2021 Mar. 12, v. 9, no. 3

2021

Abstract: Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) ... ...

Abstract	Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014–2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (p < 0.001). The findings here suggest that LF remains endemic in Sierra Leone and that caseloads are likely to resume at levels observed prior to the Ebola epidemic. The results provide insight on the current epidemiological profile of LF in Sierra Leone to facilitate LF vaccine studies and accentuate the need for LF cohort studies and continued advancements in LF diagnostics.
Keywords	Lassa virus fever ; diagnostic techniques ; disease severity ; dry season ; hospitals ; mortality ; space and time ; vaccines ; wet season ; Sierra Leone
Language	English
Dates of publication	2021-0312
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9030586
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Article: Space-Time Trends in Lassa Fever in Sierra Leone by ELISA Serostatus, 2012-2019.

Microorganisms

2021 Volume 9, Issue 3

Abstract	Lassa fever (LF) is a viral hemorrhagic disease found in Sub-Saharan Africa and is responsible for up to 300,000 cases and 5000 deaths annually. LF is highly endemic in Sierra Leone, particularly in its Eastern Province. Kenema Government Hospital (KGH) maintains one of only a few LF isolation facilities in the world with year-round diagnostic testing. Here we focus on space-time trends for LF occurring in Sierra Leone between 2012 and 2019 to provide a current account of LF in the wake of the 2014-2016 Ebola epidemic. Data were analyzed for 3277 suspected LF cases and classified as acute, recent, and non-LF or prior LF exposure using enzyme-linked immunosorbent assays (ELISAs). Presentation rates for acute, recent, and non-LF or prior LF exposure were 6.0% (195/3277), 25.6% (838/3277), and 68.4% (2244/3277), respectively. Among 2051 non-LF or prior LF exposures, 33.2% (682/2051) tested positive for convalescent LF exposure. The overall LF case-fatality rate (CFR) was 78.5% (106/135). Both clinical presentations and confirmed LF cases declined following the Ebola epidemic. These declines coincided with an increased duration between illness onset and clinical presentation, perhaps suggesting more severe disease or presentation at later stages of illness. Acute LF cases and their corresponding CFRs peaked during the dry season (November to April). Subjects with recent (but not acute) LF exposure were more likely to present during the rainy season (May to October) than the dry season (
Language	English
Publishing date	2021-03-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms9030586
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Article ; Online: Myeloid cell-driven nonregenerative pulmonary scarring is conserved in multiple nonhuman primate species regardless of SARS-CoV-2 infection modality

bioRxiv

Abstract: The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We ... ...

Abstract	The novel coronavirus SARS-CoV-2 has caused a worldwide pandemic resulting in widespread efforts in development of animal models that recapitulate human disease for evaluation of medical countermeasures, and to dissect COVID-19 immunopathogenesis. We tested whether route of experimental infection substantially changes COVID-19 disease characteristics in two species (Macaca mulatta; rhesus macaques; RM, Chlorocebus atheiops; African green monkeys; AGM) of nonhuman primates. Species-specific cohorts of RM and AGM Rhesus macaques (Macaca mulatta, RMs) and African green monkeys (Chlorocebus aethiops, AGMs) were experimentally infected with homologous SARS-CoV-2 by either direct mucosal instillation or small particle aerosol in route-discrete subcohorts. Both species demonstrated equivalent infection initially by either exposure route although the magnitude and duration of viral loading was greater in AGMs than that of the RM. Clinical onset was nearly immediate (+1dpi) in mucosally-exposed cohorts whereas aerosol-infected animals began to show signs +7dpi. Myeloid cell responses indicative of the development of pulmonary scarring and extended lack of regenerative capacity in the pulmonary compartment was a conserved pathologic response in both species by either exposure modality. This pathological commonality may be useful in future anti-fibrosis therapeutic evaluations and expands our understanding of how SARS-CoV-2 infection leads to ARDS and functional lung damage.
Keywords	covid19
Language	English
Publishing date	2021-11-30
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2021.11.28.470250
Database	COVID19

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Article: Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans

Borrega, Rodrigo / Nelson, Diana K. S. / Koval, Anatoliy P. / Bond, Nell G. / Heinrich, Megan L. / Rowland, Megan M. / Lathigra, Raju / Bush, Duane J. / Aimukanova, Irina / Phinney, Whitney N. / Koval, Sophia A. / Hoffmann, Andrew R. / Smither, Allison R. / Bell-Kareem, Antoinette R. / Melnik, Lilia I. / Genemaras, Kaylynn J. / Chao, Karissa / Snarski, Patricia / Melton, Alexandra B. /

Viruses. 2021 Nov. 21, v. 13, no. 11

2021

Abstract: Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing ... ...

Abstract	Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.
Keywords	COVID-19 infection ; Lassa virus fever ; Pseudovirus ; Severe acute respiratory syndrome coronavirus 2 ; blood ; cross immunity ; epitopes ; pandemic ; Sierra Leone
Language	English
Dates of publication	2021-1121
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112325
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Article ; Online: Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.

Borrega, Rodrigo / Nelson, Diana K S / Koval, Anatoliy P / Bond, Nell G / Heinrich, Megan L / Rowland, Megan M / Lathigra, Raju / Bush, Duane J / Aimukanova, Irina / Phinney, Whitney N / Koval, Sophia A / Hoffmann, Andrew R / Smither, Allison R / Bell-Kareem, Antoinette R / Melnik, Lilia I / Genemaras, Kaylynn J / Chao, Karissa / Snarski, Patricia / Melton, Alexandra B /

Viruses

2021 Volume 13, Issue 11

Abstract	Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.
MeSH term(s)	Age Distribution ; Alphacoronavirus/immunology ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Betacoronavirus/immunology ; Blood Donors ; COVID-19/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; Cross Protection ; Cross Reactions ; Epitopes ; Female ; Humans ; Male ; Middle East Respiratory Syndrome Coronavirus/immunology ; Phosphoproteins/immunology ; SARS-CoV-2/immunology ; Sierra Leone ; United States ; Viral Pseudotyping
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Antigens, Viral ; Coronavirus Nucleocapsid Proteins ; Epitopes ; Phosphoproteins ; nucleocapsid phosphoprotein, SARS-CoV-2
Language	English
Publishing date	2021-11-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13112325
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Article ; Online: Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages.

Heinrich, Megan L / Boisen, Matthew L / Nelson, Diana K S / Bush, Duane J / Cross, Robert W / Koval, Anatoliy P / Hoffmann, Andrew R / Beddingfield, Brandon J / Hastie, Kathryn M / Rowland, Megan M / Aimukanova, Irina / Koval, Sophia / Lathigra, Raju / Borisevich, Viktoriya / Momoh, Mambu / Sandi, John Demby / Goba, Augustine / Odia, Lkponmwosa / Baimba, Francis /

Aiyepada, John O / Ebo, Benevolence / Eromon, Philomena / Ugwu, Chinedu / Folarin, Onikepe / Olumade, Testimony / Onyechi, MacDonald N / Etafo, Johnson / Adeyemi, Rashidat / Ella, Elijah E / Aminu, Maryam / Gomerep, Simji S / Eke, Matthew Afam / Ogunsanya, Olusola / Akpede, George O / Asogun, Danny O / Okogbenin, Sylvanus A / Okokhere, Peter O / Holst, Johan / Shaffer, Jeffrey G / Schieffelin, John S / Geisbert, Thomas W / Saphire, Erica Ollmann / Happi, Christian T / Grant, Donald S / Garry, Robert F / Branco, Luis M

Scientific reports

2020 Volume 10, Issue 1, Page(s) 16030

Abstract: Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) ...

Abstract	Lassa virus (LASV) is the causative agent of Lassa fever, an often-fatal hemorrhagic disease that is endemic in West Africa. Seven genetically distinct LASV lineages have been identified. As part of CEPI's (Coalition for Epidemic Preparedness Innovations) Lassa vaccine development program, we assessed the potential of the human immune system to mount cross-reactive and cross-protective humoral immune responses to antigens from the most prevalent LASV lineages, which are lineages II and III in Nigeria and lineage IV in Sierra Leone. IgG and IgM present in the blood of Lassa fever survivors from Nigeria or Sierra Leone exhibited substantial cross-reactivity for binding to LASV nucleoprotein and two engineered (linked and prefusion) versions of the glycoproteins (GP) of lineages II-IV. There was less cross-reactivity for the Zinc protein. Serum or plasma from Nigerian Lassa fever survivors neutralized LASV pseudoviruses expressing lineage II GP better than they neutralized lineage III or IV GP expressing pseudoviruses. Sierra Leonean survivors did not exhibit a lineage bias. Neutralization titres determined using LASV pseudovirus assays showed significant correlation with titres determined by plaque reduction with infectious LASV. These studies provide guidance for comparison of humoral immunity to LASV of distinct lineages following natural infection or immunization.
MeSH term(s)	Antibodies/immunology ; Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Cross Reactions/immunology ; Genetic Variation ; Humans ; Immunity, Humoral ; Immunization ; Lassa Fever/immunology ; Lassa virus/immunology ; Lassa virus/pathogenicity ; Nigeria/epidemiology ; Nucleoproteins ; Recombinant Proteins ; Sierra Leone/epidemiology ; Survivors
Chemical Substances	Antibodies ; Antibodies, Viral ; Antigens, Viral ; Nucleoproteins ; Recombinant Proteins
Language	English
Publishing date	2020-09-29
Publishing country	England
Document type	Journal Article ; 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/s41598-020-72539-w
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