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Article: Data set on Lassa fever in post-conflict Sierra Leone

Shaffer, Jeffrey G. / Schieffelin, John S. / Grant, Donald S. / Goba, Augustine / Momoh, Mambu / Kanneh, Lansana / Levy, Danielle C. / Hartnett, Jessica N. / Boisen, Matt L. / Branco, Luis M. / Garry, Robert F.

Data in Brief. 2019 Apr., v. 23

2019

Abstract: Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the ... ...

Institution	the Viral Hemorrhagic Fever Consortium
Abstract	Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the epidemiology of Lassa fever in Sierra Leone following a decade-long civil war that ended in 2002. The data were collected at Kenema Government Hospital (KGH) in Kenema, Sierra Leone, which maintains the country׳s only Lassa fever treatment facility and a biosafety level 3 (BSL-3) laboratory. The key data set variables include Lassa fever serostatus determined using antigen (Ag), immunoglobulin M (IgM), and immunoglobulin G (IgG) ELISA diagnostic techniques; and patient demographics, survival outcome, and treatment (ribavirin) status. The individual data used to generate the graphs and tables in the corresponding research manuscript published in PLOS Neglected Tropical Diseases in 2014 and its coding guide are provided as Supplementary material (Shaffer et al., 2014) [1].
Keywords	Lassa virus fever ; antigens ; biosafety ; data collection ; demographic statistics ; hospitals ; immunoglobulin G ; patients ; Guinea ; Nigeria ; Sierra Leone
Language	English
Dates of publication	2019-04
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	2786545-9
ISSN	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.01.021
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Data set on Lassa fever in post-conflict Sierra Leone.

Shaffer, Jeffrey G / Schieffelin, John S / Grant, Donald S / Goba, Augustine / Momoh, Mambu / Kanneh, Lansana / Levy, Danielle C / Hartnett, Jessica N / Boisen, Matt L / Branco, Luis M / Garry, Robert F

Data in brief

2019 Volume 23, Page(s) 103673

Abstract	Lassa fever is a rodent-borne illness that is endemic to parts of sub-Saharan Africa, including Sierra Leone, Nigeria, and Guinea. The disease is named after the town of Lassa, Nigeria where it was discovered in 1969. This data article focuses on the epidemiology of Lassa fever in Sierra Leone following a decade-long civil war that ended in 2002. The data were collected at Kenema Government Hospital (KGH) in Kenema, Sierra Leone, which maintains the country׳s only Lassa fever treatment facility and a biosafety level 3 (BSL-3) laboratory. The key data set variables include Lassa fever serostatus determined using antigen (Ag), immunoglobulin M (IgM), and immunoglobulin G (IgG) ELISA diagnostic techniques; and patient demographics, survival outcome, and treatment (ribavirin) status. The individual data used to generate the graphs and tables in the corresponding research manuscript published in
Language	English
Publishing date	2019-01-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2786545-9
ISSN	2352-3409 ; 2352-3409
ISSN (online)	2352-3409
ISSN	2352-3409
DOI	10.1016/j.dib.2019.01.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A medical records and data capture and management system for Lassa fever in Sierra Leone: Approach, implementation, and challenges.

Shaffer, Jeffrey G / Schieffelin, John S / Gbakie, Michael / Alhasan, Foday / Roberts, Nicole B / Goba, Augustine / Randazzo, Jessica / Momoh, Mambu / Moon, Troy D / Kanneh, Lansana / Levy, Danielle C / Podgorski, Rachel M / Hartnett, Jessica N / Boisen, Matt L / Branco, Luis M / Samuels, Robert / Grant, Donald S / Garry, Robert F

PloS one

2019 Volume 14, Issue 3, Page(s) e0214284

Abstract: Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world's only Lassa fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility during the 2014 EVD outbreak. Since 2006, the Viral ... ...

Abstract	Situated in southeastern Sierra Leone, Kenema Government Hospital (KGH) maintains one of the world's only Lassa fever isolation wards and was a strategic Ebola virus disease (EVD) treatment facility during the 2014 EVD outbreak. Since 2006, the Viral Hemorrhagic Fever Consortium (VHFC) has carried out research activities at KGH, capturing clinical and laboratory data for suspected cases of Lassa fever. Here we describe the approach, progress, and challenges in designing and maintaining a data capture and management system (DCMS) at KGH to assist infectious disease researchers in building and sustaining DCMS in low-resource environments. Results on screening patterns and case-fatality rates are provided to illustrate the context and scope of the DCMS covered in this study. A medical records system and DCMS was designed and implemented between 2010 and 2016 linking historical and prospective Lassa fever data sources across KGH Lassa fever units and its peripheral health units. Data were captured using a case report form (CRF) system, enzyme-linked immunosorbent assay (ELISA) plate readers, polymerase chain reaction (PCR) machines, blood chemistry analyzers, and data auditing procedures. Between 2008 and 2016, blood samples for 4,229 suspected Lassa fever cases were screened at KGH, ranging from 219 samples in 2008 to a peak of 760 samples in 2011. Lassa fever case-fatality rates before and following the Ebola outbreak were 65.5% (148/226) and 89.5% (17/19), respectively, suggesting that fewer, but more seriously ill subjects with Lassa fever presented to KGH following the 2014 EVD outbreak (p = .040). DCMS challenges included weak specificity of the Lassa fever suspected case definition, limited capture of patient survival outcome data, internet costs, lapses in internet connectivity, low bandwidth, equipment and software maintenance, lack of computer teaching laboratories, and workload fluctuations due to variable screening activity. DCMS are the backbone of international research efforts and additional literature is needed on the topic for establishing benchmarks and driving goal-based approaches for its advancement in developing countries.
MeSH term(s)	Antibodies, Viral/blood ; Blood Chemical Analysis ; Databases, Factual ; Disease Outbreaks ; Hospitals, District ; Humans ; Information Dissemination ; Lassa Fever/diagnosis ; Lassa Fever/epidemiology ; Lassa Fever/mortality ; Lassa virus/genetics ; Lassa virus/immunology ; Lassa virus/isolation & purification ; Medical Records ; RNA, Viral/metabolism ; Sierra Leone/epidemiology ; Software ; Survival Rate
Chemical Substances	Antibodies, Viral ; RNA, Viral
Language	English
Publishing date	2019-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0214284
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Emerging trends in Lassa fever

Branco Luis M / Grove Jessica N / Boisen Matt L / Shaffer Jeffrey G / Goba Augustine / Fullah Mohammed / Momoh Mambu / Grant Donald S / Garry Robert F

Virology Journal, Vol 8, Iss 1, p

redefining the role of immunoglobulin M and inflammation in diagnosing acute infection

2011 Volume 478

Abstract: Abstract Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab- ... ...

Abstract	Abstract Background Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.
Keywords	Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-10-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome

Fonnie Mbalu / Schoepp Randal J / Bangura James J / Robinson James E / Schieffellin John S / Henderson Lee A / Muncy Ivana J / Boisen Matt L / Grove Jessica N / Branco Luis M / Hensley Lisa E / Seisay Alhassan / Fair Joseph N / Garry Robert F

Virology Journal, Vol 8, Iss 1, p

Case Report

2011 Volume 314

Abstract: Abstract Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and ... ...

Abstract	Abstract Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.
Keywords	Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	360
Language	English
Publishing date	2011-06-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Emerging trends in Lassa fever: redefining the role of immunoglobulin M and inflammation in diagnosing acute infection.

Branco, Luis M / Grove, Jessica N / Boisen, Matt L / Shaffer, Jeffrey G / Goba, Augustine / Fullah, Mohammed / Momoh, Mambu / Grant, Donald S / Garry, Robert F

Virology journal

2011 Volume 8, Page(s) 478

Abstract: Background: Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ... ...

Abstract	Background: Lassa fever (LF) is a devastating hemorrhagic viral disease that is endemic to West Africa and responsible for thousands of human deaths each year. Analysis of humoral immune responses (IgM and IgG) by antibody-capture ELISA (Ab-capture ELISA) and Lassa virus (LASV) viremia by antigen-capture ELISA (Ag-capture ELISA) in suspected patients admitted to the Kenema Government Hospital (KGH) Lassa Fever Ward (LFW) in Sierra Leone over the past five years is reshaping our understanding of acute LF. Results: Analyses in LF survivors indicated that LASV-specific IgM persists for months to years after initial infection. Furthermore, exposure to LASV appeared to be more prevalent in historically non-endemic areas of West Africa with significant percentages of reportedly healthy donors IgM and IgG positive in LASV-specific Ab-capture ELISA. We found that LF patients who were Ag positive were more likely to die than suspected cases who were only IgM positive. Analysis of metabolic and immunological parameters in Ag positive LF patients revealed a strong correlation between survival and low levels of IL-6, -8, -10, CD40L, BUN, ALP, ALT, and AST. Despite presenting to the hospital with fever and in some instances other symptoms consistent with LF, the profiles of Ag negative IgM positive individuals were similar to those of normal donors and nonfatal (NF) LF cases, suggesting that IgM status cannot necessarily be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. Conclusion: Only LASV viremia assessed by Ag-capture immunoassay, nucleic acid detection or virus isolation should be used to diagnose acute LASV infection in West Africans. LASV-specific IgM serostatus cannot be considered a diagnostic marker of acute LF in suspected cases living in endemic areas of West Africa. By applying these criteria, we identified a dysregulated metabolic and pro-inflammatory response profile conferring a poor prognosis in acute LF. In addition to suggesting that the current diagnostic paradigm for acute LF should be reconsidered, these studies present new opportunities for therapeutic interventions based on potential prognostic markers in LF.
MeSH term(s)	Adolescent ; Adult ; Antibodies, Viral/blood ; Antigens, Viral/blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunoglobulin M/blood ; Inflammation/pathology ; Lassa Fever/diagnosis ; Lassa Fever/immunology ; Lassa Fever/pathology ; Lassa virus/immunology ; Lassa virus/pathogenicity ; Male ; RNA, Viral/blood ; Sierra Leone ; Viremia/diagnosis ; Virus Cultivation ; Young Adult
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Immunoglobulin M ; RNA, Viral
Language	English
Publishing date	2011-10-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/1743-422X-8-478
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever

Branco, Luis M / Grove, Jessica N / Geske, Frederick J / Boisen, Matt L / Muncy, Ivana J / Magliato, Susan A / Henderson, Lee A / Schoepp, Randal J / Cashman, Kathleen A / Hensley, Lisa E / Garry, Robert F

Virology journal. 2010 Dec., v. 7, no. 1

2010

Abstract: BACKGROUND: Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully ... ...

Abstract	BACKGROUND: Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine platform. RESULTS: A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. CONCLUSIONS: These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.
Keywords	Lassa mammarenavirus ; Lassa virus fever ; RNA ; biosafety ; commercialization ; electron microscopy ; epitopes ; fever ; glycoproteins ; glycosylation ; health services ; humans ; intravenous injection ; nucleoproteins ; oral administration ; polypeptides ; ribosomes ; tropical diseases ; vaccination ; vaccines ; virion ; virology ; viruses
Language	English
Dates of publication	2010-12
Size	p. 279.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	2160640-7
ISSN	1743-422X
ISSN	1743-422X
DOI	10.1186/1743-422X-7-279
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever

Cashman Kathleen A / Henderson Lee A / Schoepp Randal J / Magliato Susan A / Muncy Ivana J / Boisen Matt L / Geske Frederick J / Grove Jessica N / Branco Luis M / Hensley Lisa E / Garry Robert F

Virology Journal, Vol 7, Iss 1, p

2010 Volume 279

Abstract: Abstract Background Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully ...

Abstract	Abstract Background Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine platform. Results A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. Conclusions These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.
Keywords	Microbiology ; QR1-502 ; Science ; Q ; DOAJ:Microbiology ; DOAJ:Biology ; DOAJ:Biology and Life Sciences ; Medicine (General) ; R5-920 ; Medicine ; R ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	616
Language	English
Publishing date	2010-10-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lassa virus-like particles displaying all major immunological determinants as a vaccine candidate for Lassa hemorrhagic fever.

Virology journal

2010 Volume 7, Page(s) 279

Abstract: Background: Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully ... ...

Abstract	Background: Lassa fever is a neglected tropical disease with significant impact on the health care system, society, and economy of Western and Central African nations where it is endemic. Treatment of acute Lassa fever infections has successfully utilized intravenous administration of ribavirin, a nucleotide analogue drug, but this is not an approved use; efficacy of oral administration has not been demonstrated. To date, several potential new vaccine platforms have been explored, but none have progressed toward clinical trials and commercialization. Therefore, the development of a robust vaccine platform that could be generated in sufficient quantities and at a low cost per dose could herald a subcontinent-wide vaccination program. This would move Lassa endemic areas toward the control and reduction of major outbreaks and endemic infections. To this end, we have employed efficient mammalian expression systems to generate a Lassa virus (LASV)-like particle (VLP)-based modular vaccine platform. Results: A mammalian expression system that generated large quantities of LASV VLP in human cells at small scale settings was developed. These VLP contained the major immunological determinants of the virus: glycoprotein complex, nucleoprotein, and Z matrix protein, with known post-translational modifications. The viral proteins packaged into LASV VLP were characterized, including glycosylation profiles of glycoprotein subunits GP1 and GP2, and structural compartmentalization of each polypeptide. The host cell protein component of LASV VLP was also partially analyzed, namely glycoprotein incorporation, though the identity of these proteins remain unknown. All combinations of LASV Z, GPC, and NP proteins that generated VLP did not incorporate host cell ribosomes, a known component of native arenaviral particles, despite detection of small RNA species packaged into pseudoparticles. Although VLP did not contain the same host cell components as the native virion, electron microscopy analysis demonstrated that LASV VLP appeared structurally similar to native virions, with pleiomorphic distribution in size and shape. LASV VLP that displayed GPC or GPC+NP were immunogenic in mice, and generated a significant IgG response to individual viral proteins over the course of three immunizations, in the absence of adjuvants. Furthermore, sera from convalescent Lassa fever patients recognized VLP in ELISA format, thus affirming the presence of native epitopes displayed by the recombinant pseudoparticles. Conclusions: These results established that modular LASV VLP can be generated displaying high levels of immunogenic viral proteins, and that small laboratory scale mammalian expression systems are capable of producing multi-milligram quantities of pseudoparticles. These VLP are structurally and morphologically similar to native LASV virions, but lack replicative functions, and thus can be safely generated in low biosafety level settings. LASV VLP were immunogenic in mice in the absence of adjuvants, with mature IgG responses developing within a few weeks after the first immunization. These studies highlight the relevance of a VLP platform for designing an optimal vaccine candidate against Lassa hemorrhagic fever, and warrant further investigation in lethal challenge animal models to establish their protective potential.
MeSH term(s)	Animals ; Antibodies, Viral/blood ; Antigens, Viral/genetics ; Antigens, Viral/immunology ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunization, Secondary/methods ; Immunoglobulin G/blood ; Lassa Fever/immunology ; Lassa Fever/prevention & control ; Lassa virus/genetics ; Lassa virus/immunology ; Mice ; Mice, Inbred BALB C ; Vaccination/methods ; Vaccines, Synthetic/genetics ; Vaccines, Synthetic/immunology ; Vaccines, Virosome/genetics ; Vaccines, Virosome/immunology ; Viral Proteins/genetics ; Viral Proteins/immunology ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Viral ; Antigens, Viral ; Immunoglobulin G ; Vaccines, Synthetic ; Vaccines, Virosome ; Viral Proteins ; Viral Vaccines
Language	English
Publishing date	2010-10-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/1743-422X-7-279
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Capacity building permitting comprehensive monitoring of a severe case of Lassa hemorrhagic fever in Sierra Leone with a positive outcome: case report.

Grove, Jessica N / Branco, Luis M / Boisen, Matt L / Muncy, Ivana J / Henderson, Lee A / Schieffellin, John S / Robinson, James E / Bangura, James J / Fonnie, Mbalu / Schoepp, Randal J / Hensley, Lisa E / Seisay, Alhassan / Fair, Joseph N / Garry, Robert F

Virology journal

2011 Volume 8, Page(s) 314

Abstract: Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular ... ...

Abstract	Lassa fever is a neglected tropical disease with a significant impact on the health care system of endemic West African nations. To date, case reports of Lassa fever have focused on laboratory characterisation of serological, biochemical and molecular aspects of the disease imported by infected individuals from Western Africa to the United States, Canada, Europe, Japan and Israel. Our report presents the first comprehensive real time diagnosis and characterization of a severe, hemorrhagic Lassa fever case in a Sierra Leonean individual admitted to the Kenema Government Hospital Lassa Fever Ward. Fever, malaise, unresponsiveness to anti-malarial and antibiotic drugs, followed by worsening symptoms and onset of haemorrhaging prompted medical officials to suspect Lassa fever. A recombinant Lassa virus protein based diagnostic was employed in diagnosing Lassa fever upon admission. This patient experienced a severe case of Lassa hemorrhagic fever with dysregulation of overall homeostasis, significant liver and renal system involvement, the interplay of pro- and anti-inflammatory cytokines during the course of hospitalization and an eventual successful outcome. These studies provide new insights into the pathophysiology and management of this viral illness and outline the improved infrastructure, research and real-time diagnostic capabilities within LASV endemic areas.
MeSH term(s)	Adult ; Aged ; Antibodies, Viral/blood ; Antigens, Viral/blood ; Capacity Building ; Child ; Clinical Laboratory Techniques/methods ; Contact Tracing ; Female ; Humans ; Immunoassay/methods ; Lassa Fever/diagnosis ; Lassa Fever/pathology ; Lassa virus/isolation & purification ; Male ; Pregnancy ; Sierra Leone ; Treatment Outcome ; Young Adult
Chemical Substances	Antibodies, Viral ; Antigens, Viral
Language	English
Publishing date	2011-06-20
Publishing country	England
Document type	Case Reports ; 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	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/1743-422X-8-314
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Inter-library loan at ZB MED

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Order via subito

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Order via subito