Post-Exposure Protection in Mice against Sudan Virus by a Two Antibody Cocktail.
Viruses
; 10(6)2018 05 26.
Article
em En
| MEDLINE
| ID: mdl-29861435
ABSTRACT
Sudan virus (SUDV) and Ebola viruses (EBOV) are both members of the Ebolavirus genus and have been sources of epidemics and outbreaks for several decades. We present here the generation and characterization of cross-reactive antibodies to both SUDV and EBOV, which were produced in a cell-free system and protective against SUDV in mice. A non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of SUDV-Boniface (8A). Two separate antibody fragment phage display libraries were constructed after four immunogen injections. Both libraries were screened first against the SUDV and a second library was cross-selected against EBOV-Kikwit. Sequencing of 288 selected clones from the two distinct libraries identified 58 clones with distinct VH and VL sequences. Many of these clones were cross-reactive to EBOV and SUDV and able to neutralize SUDV. Three of these recombinant antibodies (X10B1, X10F3, and X10H2) were produced in the scFv-Fc format utilizing a cell-free production system. Mice that were challenged with SUDV-Boniface receiving 100µg of the X10B1/X10H2 scFv-Fc combination 6 and 48-h post-exposure demonstrated partial protection individually and complete protection as a combination. The data herein suggests these antibodies may be promising candidates for further therapeutic development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Proteínas da Matriz Viral
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Doença pelo Vírus Ebola
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Ebolavirus
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Profilaxia Pós-Exposição
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Vacinas de Partículas Semelhantes a Vírus
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Anticorpos Antivirais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Viruses
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos