Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses

Swenson, Dana L.; Warfield, Kelly L.; Larsen, Tom; Alves, Derron A.; Coberley, Sadie S.; Bavari, Sina

doi:10.1586/14760584.7.4.417

Cited by 70 publications

(72 citation statements)

References 35 publications

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“…These vaccines completely protected NHPs against lethal disease and are mostly replication-defective or replication-competent viral vectors, including alphavirus replicons 241,242 , human adenoviruses [243][244][245][246][247] , chimpanzee adenoviruses 248 , paramyxoviruses 249,250 , rabies viruses 251,252 and several different strategies with recombinant vesicular stomatitis viruses (rVSVs), including both the prototype rVSV vaccine [253][254][255][256][257] and a newer rVSV vaccine developed for enhanced safety (VesiculoVax) 258 . Virus-like particles [259][260][261] , a biologically contained EBOV lacking viral protein 30 (VP30) 262 , DNA 244 and several combinations of vaccines that include DNA, modified vaccinia Ankara (MVA) and various adenoviruses can also completely protect NHPs from lethal filovirus disease 244,248,263 .…”

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

“…There is no cross protection between members of the genus Marburgvirus and members of the genus Ebolavirus. Within the genus Marburgvirus, several vaccines protect cynomolgus monkeys against both Marburg virus (MARV) and Ravn virus (RAVV) 254,261 . For the Ebolavirus genus, there is limited cross protection among the various species with the use of GP-based vaccines.…”

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

“…The filovirus replication cycle is outlined in FIG. 1 254,261 . For the Ebolavirus genus, there is limited cross protection among the various species with the use of GP-based vaccines.…”

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confidence: 99%

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Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

Section: Box 2 | Vaccination To Prevent Filovirus Infectionmentioning

confidence: 99%

See 1 more Smart Citation

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

107

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“…3 and 4) indicated additional similarities to filovirus disease observed in other models, including guinea pigs and nonhuman primates (10, 16, 24, 29, 34, 40-43, 45-47, 50, 54). Principle gross necropsy lesions in guinea pigs and nonhuman primates after MARV infection include splenomegaly, enlarged fatty liver, enlarged mesenteric lymph nodes, consolidated hemorrhagic areas in the lungs, and vascular congestion and petechial and/or ecchymotic hemorrhage in the gastrointestinal tract, reproductive organs, adrenal glands, pancreas, liver, spleen, brain, and heart (24,32,34,40,45,49,51,54). Initial microscopic lesions in MARV-infected guinea pigs and nonhuman primates arise in the mononuclear phagocytic system of the liver and spleen (24,32,34,40,45,54).…”

Section: Vol 83 2009 Novel Mouse Model For Marburgvirus 6409mentioning

confidence: 99%

Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

Warfield

Bradfute

Wells

et al. 2009

J Virol

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152

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The lack of a mouse model has hampered an understanding of the pathogenesis and immunity of Marburg hemorrhagic fever (MHF), the disease caused by marburgvirus (MARV), and has created a bottleneck in the development of antiviral therapeutics. Primary isolates of the filoviruses, i.e., ebolavirus (EBOV) and MARV, are not lethal to immunocompetent adult mice. Previously, pathological, virologic, and immunologic evaluation of a mouse-adapted EBOV, developed by sequential passages in suckling mice, identified many similarities between this model and EBOV infections in nonhuman primates. We recently demonstrated that serially passaging virus recovered from the liver homogenates of MARV-infected immunodeficient (SCID) mice was highly successful in reducing the time to death in these mice from 50 to 70 days to 7 to 10 days after challenge with the isolate MARV-Ci67, -Musoke, or -Ravn. In this study, we extended our findings to show that further sequential passages of MARV-Ravn in immunocompetent mice caused the MARV to kill BALB/c mice. Serial sampling studies to characterize the pathology of mouse-adapted MARV-Ravn revealed that this model is similar to the guinea pig and nonhuman primate MHF models. Infection of BALB/c mice with mouse-adapted MARV-Ravn caused uncontrolled viremia and high viral titers in the liver, spleen, lymph node, and other organs; profound lymphopenia; destruction of lymphocytes within the spleen and lymph nodes; and marked liver damage and thrombocytopenia. Sequencing the mouse-adapted MARV-Ravn strain revealed differences in 16 predicted amino acids from the progenitor virus, although the exact changes required for adaptation are unclear at this time. This mouse-adapted MARV strain can now be used to develop and evaluate novel vaccines and therapeutics and may also help to provide a better understanding of the virulence factors associated with MARV.

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“…В качестве основных направлений создания эф-фективных вакцин для этих нозологических форм ранее рассматривали цельновирионные убитые вак-цины, вирусоподобные частицы, ДНК-вакцины, век-торные рекомбинантные вакцины на основе аденови-русов и вируса везикулярного стоматита [4, 5, 11,15,19,25, 28,29, 33, 34].…”

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Future Developments and Applications of the Vaccines against Dangerous Viral Infections, RNA-Replicon-Based, Obtained from the Venezuelan Equine Encephalomyelitis Virus

Petrov¹,

Лебедев²,

Plekhanova³

et al. 2014

Problemy Osobo Opasnykh Infektsii

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Проблемы особо опасных инфекций, вып. 3, 2014 86 Представители семейств Filoviridae (вирусы Марбург, Эбола) и Arenaviridae (вирусы Ласса, Луйо, Мачупо, Хунин, Гуанорито, Сэбиа) являются этио-логическими агентами особо опасных вирусных ге-моррагических лихорадок (ООВГЛ). Они вызывают острые заболевания человека, характеризующиеся шоком, геморрагиями, мультиорганной недостаточ-ностью, и заканчиваются летальным исходом в 22-90 % случаев [9,20, 21].Данные возбудители рассматриваются как угроза здравоохранению вследствие их неконтролируемого завоза в неэндемичные регионы, поэтому вопрос о создании специфических медицинских средств за-щиты в отношении вызываемых ими заболеваний является актуальным. Вакцинация групп риска явля-ется наиболее эффективным и экономичным спосо-бом защиты от эпидемии, которая может возникнуть в результате завоза возбудителя [3, 7, 8,15].В качестве основных направлений создания эф-фективных вакцин для этих нозологических форм ранее рассматривали цельновирионные убитые вак-цины, вирусоподобные частицы, ДНК-вакцины, век-торные рекомбинантные вакцины на основе аденови-русов и вируса везикулярного стоматита [4, 5, 11,15,19,25, 28,29, 33, 34].Следует подчеркнуть, что идеальная вакцина должна вызывать долговременный иммунитет при однократном введении, обладать перекрестной ре-активностью к различным природным штаммам воз-будителя и не вызывать поствакцинальных осложне-ний. Кроме того, стоимость вакцины не должна пре-пятствовать ее массовому применению. Представители семейства Filoviridae (вирусы Марбург, Эбола) и Arenaviridae (вирусы Ласса, Луйо, Мачупо, Хунин, Гуанарито, Сэбиа) являются этиологическими агентами особо опасных вирусных геморрагических лихо-радок. Данные возбудители представляют потенциальную угрозу для здравоохранения вследствие возможности их случайного завоза в неэндемичные регионы, поэтому актуальным является вопрос о создании специфических медицинских средств защиты в отношении вызываемых ими заболеваний. По мнению ведущих специалистов, вакцинация групп риска является наиболее эффективным и экономичным способом защиты от развития эпиде-мии. В обзоре рассмотрено новое перспективное направление разработки защитных препаратов в отношении особо опасных вирусных инфекций -создание вакцин на основе репликонов альфавирусов. Разработка рекомби-нантных репликонов не требует культивирования патогенных микроорганизмов. Особенностью РНК-репликонов является их неспособность продуцировать инфекционное потомство, что имеет особое значение при создании вакцин в отношении особо опасных вирусных геморрагических лихорадок. Преимущества альфавирусных ре-пликонов перед другими РНК-репликонами при разработке вакцин заключаются в высоком уровне экспрессии гетерологичных генов и резистентности к анти-векторному иммунитету. РНК-репликоны альфавирусов сочета-ют безопасность инактивированных и иммуногенность живых аттенуированных вакцин. Репликоны на основе альфавирусов пригодны для экспрессной разработки вакцин с целью специфической профилактики вирусных инфекционных заболеваний.Ключевые слова: вирус ...

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Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses

Cited by 70 publications

References 35 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Development and Characterization of a Mouse Model for Marburg Hemorrhagic Fever

Future Developments and Applications of the Vaccines against Dangerous Viral Infections, RNA-Replicon-Based, Obtained from the Venezuelan Equine Encephalomyelitis Virus

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