Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges

Caleb D. Marceau, Surendra S. Negi, Humberto Hernandez, Julie Callison, Andrea Marzi, Viktoriya Borisevich, Werner Braun, Jody Berry, Heinz Feldmann, Barry Rockx

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Filoviruses are the causative agents of lethal hemorrhagic fever in human and non-human primates (NHP). The family of Filoviridae is composed of three genera, Ebolavirus, Marburgvirus and Cuevavirus. There are currently no approved vaccines or antiviral therapeutics for the treatment of filovirus infections in humans. Passive transfer of neutralizing antibodies targeting the Ebola virus (EBOV) glycoprotein (GP) has proven effective in protecting mice, guinea pigs and NHP from lethal challenges with EBOV. In this study, we generated two neutralizing monoclonal antibodies (MAbs), termed S9 and M4 that recognize the GP of EBOV or multiple strains of Marburg virus (MARV), respectively. We characterized the putative binding site of S9 as a linear epitope on the glycan cap of the GP1 subunit of the EBOV-GP. The M4 antibody recognizes an unknown conformational epitope on MARV-GP. Additionally, we demonstrated the post-exposure protection potential of these antibodies in both the mouse and guinea pig models of filovirus infection. These data indicate that MAbs S9 and M4 would be good candidates for inclusion in an antibody cocktail for the treatment of filovirus infections.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalTrials in Vaccinology
Volume3
Issue number1
DOIs
StatePublished - 2014

Fingerprint

Ebolavirus
Neutralizing Antibodies
Marburgvirus
Rodentia
Monoclonal Antibodies
Glycoproteins
Primates
Filoviridae
Antibodies
Epitopes
Guinea Pigs
Infection
Antiviral Agents
Polysaccharides
Fever
Vaccines
Binding Sites

Keywords

  • Animal model
  • Filovirus
  • Neutralizing antibody
  • Prophylaxis

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health

Cite this

Marceau, C. D., Negi, S. S., Hernandez, H., Callison, J., Marzi, A., Borisevich, V., ... Rockx, B. (2014). Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges. Trials in Vaccinology, 3(1), 89-94. https://doi.org/10.1016/j.trivac.2014.04.002

Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges. / Marceau, Caleb D.; Negi, Surendra S.; Hernandez, Humberto; Callison, Julie; Marzi, Andrea; Borisevich, Viktoriya; Braun, Werner; Berry, Jody; Feldmann, Heinz; Rockx, Barry.

In: Trials in Vaccinology, Vol. 3, No. 1, 2014, p. 89-94.

Research output: Contribution to journalArticle

Marceau, CD, Negi, SS, Hernandez, H, Callison, J, Marzi, A, Borisevich, V, Braun, W, Berry, J, Feldmann, H & Rockx, B 2014, 'Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges', Trials in Vaccinology, vol. 3, no. 1, pp. 89-94. https://doi.org/10.1016/j.trivac.2014.04.002
Marceau, Caleb D. ; Negi, Surendra S. ; Hernandez, Humberto ; Callison, Julie ; Marzi, Andrea ; Borisevich, Viktoriya ; Braun, Werner ; Berry, Jody ; Feldmann, Heinz ; Rockx, Barry. / Novel neutralizing monoclonal antibodies protect rodents against lethal filovirus challenges. In: Trials in Vaccinology. 2014 ; Vol. 3, No. 1. pp. 89-94.
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