Characterization of neutralizing antibodies to West Nile virus

We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation dependent epitopes in domain III of the E protein. Four of th...

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Published inVirology (New York, N.Y.) Vol. 336; no. 1; pp. 70 - 82
Main Authors Sánchez, Melissa D., Pierson, Theodore C., McAllister, Douglas, Hanna, Sheri L., Puffer, Bridget A., Valentine, Laura E., Murtadha, Mariam M., Hoxie, James A., Doms, Robert W.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 25.05.2005
Subjects
Animals
Antibodies, Monoclonal - immunology
Antibodies, Viral - immunology
Antigens, Viral - immunology
Cross Reactions
disease control
Encephalitis Virus, Japanese - immunology
Encephalitis Virus, St. Louis - immunology
Encephalitis Viruses, Tick-Borne - immunology
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
epitopes
Epitopes - immunology
Flavivirus
glycoproteins
Glycoproteins - immunology
Mice
Monoclonal antibodies
Neutralization
Neutralization Tests
Protein Structure, Tertiary
viral antibodies
viral antigens
viral envelope proteins
viral proteins
West Nile virus
West Nile virus - immunology
Yellow fever virus - immunology
Monoclonal antibodies
Flavivirus
West Nile virus
Neutralization
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Abstract We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation dependent epitopes in domain III of the E protein. Four of the MAbs neutralized WNV infection and bound to the same region of domain III with high affinity. The neutralizing MAbs were obtained from mice immunized with inactivated virus alone or in combination with a DNA plasmid. In contrast, MAbs obtained by immunization with a soluble version of the E glycoprotein did not exhibit neutralizing activity. These non-neutralizing antibodies were cross-reactive with several other flaviviruses, including Saint Louis encephalitis, Japanese encephalitis, Yellow Fever and Powassan viruses. Interestingly, some non-neutralizing MAbs bound with high affinity to domains I or III, indicating that both affinity and the precise epitope recognized by an antibody are important determinants of WNV neutralization.
AbstractList We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation dependent epitopes in domain III of the E protein. Four of the MAbs neutralized WNV infection and bound to the same region of domain III with high affinity. The neutralizing MAbs were obtained from mice immunized with inactivated virus alone or in combination with a DNA plasmid. In contrast, MAbs obtained by immunization with a soluble version of the E glycoprotein did not exhibit neutralizing activity. These non-neutralizing antibodies were cross-reactive with several other flaviviruses, including Saint Louis encephalitis, Japanese encephalitis, Yellow Fever and Powassan viruses. Interestingly, some non-neutralizing MAbs bound with high affinity to domains I or III, indicating that both affinity and the precise epitope recognized by an antibody are important determinants of WNV neutralization.
Author McAllister, Douglas
Pierson, Theodore C.
Hanna, Sheri L.
Murtadha, Mariam M.
Doms, Robert W.
Sánchez, Melissa D.
Hoxie, James A.
Puffer, Bridget A.
Valentine, Laura E.
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  surname: Sánchez
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  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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  surname: Pierson
  fullname: Pierson, Theodore C.
  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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  givenname: Douglas
  surname: McAllister
  fullname: McAllister, Douglas
  organization: ViroStat, Incorporated, Portland, ME 04104, USA
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  givenname: Sheri L.
  surname: Hanna
  fullname: Hanna, Sheri L.
  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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  givenname: Bridget A.
  surname: Puffer
  fullname: Puffer, Bridget A.
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  surname: Valentine
  fullname: Valentine, Laura E.
  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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  givenname: Mariam M.
  surname: Murtadha
  fullname: Murtadha, Mariam M.
  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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  givenname: James A.
  surname: Hoxie
  fullname: Hoxie, James A.
  organization: Department of Medicine, Hematology-Oncology Division, University of Pennsylvania, Philadelphia, PA 19104, USA
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  givenname: Robert W.
  surname: Doms
  fullname: Doms, Robert W.
  email: doms@mail.med.upenn.edu
  organization: Department of Microbiology, University of Pennsylvania, 225 Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA
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Keywords Monoclonal antibodies
Flavivirus
West Nile virus
Neutralization
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Snippet We produced nine monoclonal antibodies (MAbs) directed against the West Nile virus E glycoprotein using three different immunization strategies: inactivated...
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SubjectTerms Animals
Antibodies, Monoclonal - immunology
Antibodies, Viral - immunology
Antigens, Viral - immunology
Cross Reactions
disease control
Encephalitis Virus, Japanese - immunology
Encephalitis Virus, St. Louis - immunology
Encephalitis Viruses, Tick-Borne - immunology
Enzyme-Linked Immunosorbent Assay
Epitope Mapping
epitopes
Epitopes - immunology
Flavivirus
glycoproteins
Glycoproteins - immunology
Mice
Monoclonal antibodies
Neutralization
Neutralization Tests
Protein Structure, Tertiary
viral antibodies
viral antigens
viral envelope proteins
viral proteins
West Nile virus
West Nile virus - immunology
Yellow fever virus - immunology
Title Characterization of neutralizing antibodies to West Nile virus
URI https://dx.doi.org/10.1016/j.virol.2005.02.020
https://www.ncbi.nlm.nih.gov/pubmed/15866072
https://search.proquest.com/docview/17872457
https://search.proquest.com/docview/67788021
Volume 336
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