Correction: Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs

Fusco, Marnie L.; Hanabusa, Takao; Cassan, Robyn; Biggins, Julia E.; Murin, Charles D.; Warfield, Kelly L.; Li, Sheng; Holtsberg, Frederick W.; Shulenin, Sergey; Vu, Hong; Olinger, Gene G.; Kim, Dowhan; Whaley, Kevin J.; Zeitlin, Larry; Ward, Andrew B.; Nykiforuk, Cory L.; Aman, M. Javad; Berry, Jody D.; Saphire, Erica Ollmann

doi:10.1371/journal.ppat.1005212

Cited by 7 publications

(1 citation statement)

References 1 publication

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“…Thus, mAbs CM10, CM11.1, and CM12.1 target an overlapping epitope within the GP2 N terminus, one that overlaps with epitopes of previously reported protective marburgvirus mAbs isolated from natural infection and animal immunizations ( Fig. 5E ) [14-16, 38].…”

Section: Resultsmentioning

confidence: 59%

Cross-reactive macaque antibodies targeting marburgvirus glycoprotein induced by multivalent immunization

Janus,

Wang,

Cleveland

et al. 2023

Preprint

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We utilized B cells from a Rhesus macaque immunized with a multivalent prime-boost regimen of filovirus antigens to isolate a novel panel of marburgvirus glycoprotein (GP)-specific monoclonal antibodies (mAbs). A heterologous marburgvirus GP probe was used to sort for B cells with cross-marburgvirus reactive breadth. 33 mAbs belonging to 28 unique lineages were expressed and experimentally characterized. Antibody specificities were assessed by binding competition and overlapping pepscan analyses, and were found to map to a previously characterized protective region on GP2 and a cross-filovirus reactive region on GP1, among others. A third of the lineages targeted the predicted receptor binding region (RBR), including two lineages with potent Marburg pseudovirus neutralization that were structurally analyzed and confirmed to recognize this region. Our study describes the discovery and characterization of a diverse panel of antibodies against marburgvirus GP induced by multivalent immunization and provides candidate immunotherapeutics for further study and development.

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Section: Resultsmentioning

confidence: 59%

Cross-reactive macaque antibodies targeting marburgvirus glycoprotein induced by multivalent immunization

Janus,

Wang,

Cleveland

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Macaque antibodies targeting Marburg virus glycoprotein induced by multivalent immunization

Janus,

Wang,

Cleveland

et al. 2024

J Virol

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Marburg virus infection in humans is associated with case fatality rates that can reach up to 90%, but to date, there are no approved vaccines or monoclonal antibody (mAb) countermeasures. Here, we immunized Rhesus macaques with multivalent combinations of filovirus glycoprotein (GP) antigens belonging to Marburg, Sudan, and Ebola viruses to generate monospecific and cross-reactive antibody responses against them. From the animal that developed the highest titers of Marburg virus GP-specific neutralizing antibodies, we sorted single memory B cells using a heterologous Ravn virus GP probe and cloned and characterized a panel of 34 mAbs belonging to 28 unique lineages. Antibody specificities were assessed by overlapping pepscan and binding competition analyses, revealing that roughly a third of the lineages mapped to the conserved receptor binding region, including potent neutralizing lineages that were confirmed by negative stain electron microscopy to target this region. Additional lineages targeted a protective region on GP2, while others were found to possess cross-filovirus reactivity. Our study advances the understanding of orthomarburgvirus glycoprotein antigenicity and furthers efforts to develop candidate antibody countermeasures against these lethal viruses. IMPORTANCE Marburg viruses were the first filoviruses characterized to emerge in humans in 1967 and cause severe hemorrhagic fever with average case fatality rates of ~50%. Although mAb countermeasures have been approved for clinical use against the related Ebola viruses, there are currently no approved countermeasures against Marburg viruses. We successfully isolated a panel of orthomarburgvirus GP-specific mAbs from a macaque immunized with a multivalent combination of filovirus antigens. Our analyses revealed that roughly half of the antibodies in the panel mapped to regions on the glycoprotein shown to protect from infection, including the host cell receptor binding domain and a protective region on the membrane-anchoring subunit. Other antibodies in the panel exhibited broad filovirus GP recognition. Our study describes the discovery of a diverse panel of cross-reactive macaque antibodies targeting orthomarburgvirus and other filovirus GPs and provides candidate immunotherapeutics for further study and development.

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Phylogenetic Characterization of Crimean-Congo Hemorrhagic Fever Virus Detected in African Blue Ticks Feeding on Cattle in a Ugandan Abattoir

et al. 2021

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Crimean-Congo hemorrhagic fever virus (CCHFV) is the most geographically widespread of the tick-borne viruses. However, African strains of CCHFV are poorly represented in sequence databases. In addition, almost all sequence data collected to date have been obtained from cases of human disease, while information regarding the circulation of the virus in tick and animal reservoirs is severely lacking. Here, we characterize the complete coding region of a novel CCHFV strain, detected in African blue ticks (Rhipicephalus (Boophilus) decoloratus) feeding on cattle in an abattoir in Kampala, Uganda. These cattle originated from a farm in Mbarara, a major cattle-trading hub for much of Uganda. Phylogenetic analysis indicates that the newly sequenced strain belongs to the African genotype II clade, which predominantly contains the sequences of strains isolated from West Africa in the 1950s, and South Africa in the 1980s. Whilst the viral S (nucleoprotein) and L (RNA polymerase) genome segments shared >90% nucleotide similarity with previously reported genotype II strains, the glycoprotein-coding M segment shared only 80% nucleotide similarity with the next most closely related strains, which were derived from ticks in Western India and Northern China. This genome segment also displayed a large number of non-synonymous mutations previously unreported in the genotype II strains. Characterization of this novel strain adds to our limited understanding of the natural diversity of CCHFV circulating in both ticks and in Africa. Such data can be used to inform the design of vaccines and diagnostics, as well as studies exploring the epidemiology and evolution of the virus for the establishment of future CCHFV control strategies.

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Correction: Protective mAbs and Cross-Reactive mAbs Raised by Immunization with Engineered Marburg Virus GPs

Cited by 7 publications

References 1 publication

Cross-reactive macaque antibodies targeting marburgvirus glycoprotein induced by multivalent immunization

Cross-reactive macaque antibodies targeting marburgvirus glycoprotein induced by multivalent immunization

Macaque antibodies targeting Marburg virus glycoprotein induced by multivalent immunization

Phylogenetic Characterization of Crimean-Congo Hemorrhagic Fever Virus Detected in African Blue Ticks Feeding on Cattle in a Ugandan Abattoir

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