Development of a Humanized Monoclonal Antibody with Therapeutic Potential Against West Nile Virus

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2005 Apr 27

PMID 15852016

Citations 310

Authors

Theodore Oliphant

Michael Engle

Grant E Nybakken

Chris Doane

Syd Johnson

Ling Huang

Sergey Gorlatov

Erin Mehlhop

Anantha Marri

Kyung Min Chung

Gregory D Ebel

Laura D Kramer

Daved H Fremont

Michael S Diamond

Affiliations

Soon will be listed here.

Abstract

Neutralization of West Nile virus (WNV) in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Using random mutagenesis and yeast surface display, we defined individual contact residues of 14 newly generated monoclonal antibodies against domain III of the WNV E protein. Monoclonal antibodies that strongly neutralized WNV localized to a surface patch on the lateral face of domain III. Convalescent antibodies from individuals who had recovered from WNV infection also detected this epitope. One monoclonal antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic efficacy in mice, even when administered as a single dose 5 d after infection. A humanized version of E16 was generated that retained antigen specificity, avidity and neutralizing activity. In postexposure therapeutic trials in mice, a single dose of humanized E16 protected mice against WNV-induced mortality, and may therefore be a viable treatment option against WNV infection in humans.

Citing Articles

The recombinant truncated envelope protein of West Nile virus adjuvanted with Alum/CpG induces potent humoral and T cell immunity in mice.

Du Y, Deng Y, Zhan Y, Yang R, Ren J, Wang W Biosaf Health. 2025; 5(5):300-307.

PMID: 40078908 PMC: 11894981. DOI: 10.1016/j.bsheal.2023.06.003.

Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses.

Baric T, Reneer Z Viruses. 2025; 17(1).

PMID: 39861790 PMC: 11769264. DOI: 10.3390/v17010001.

pr-independent biogenesis of infectious mature Zika virus particles.

Dowd K, Schroeder M, Sanchez E, Brumbaugh B, Foreman B, Burgomaster K bioRxiv. 2024; .

PMID: 39372759 PMC: 11452192. DOI: 10.1101/2024.09.12.612520.

Lessons Learned from West Nile Virus Infection:Vaccinations in Equines and Their Implications for One Health Approaches.

Naveed A, Eertink L, Wang D, Li F Viruses. 2024; 16(5).

PMID: 38793662 PMC: 11125849. DOI: 10.3390/v16050781.

A compendium of multi-omics data illuminating host responses to lethal human virus infections.

Eisfeld A, Anderson L, Fan S, Walters K, Halfmann P, Westhoff Smith D Sci Data. 2024; 11(1):328.

PMID: 38565538 PMC: 10987564. DOI: 10.1038/s41597-024-03124-3.

References

Granwehr B, Lillibridge K, Higgs S, Mason P, Aronson J, Campbell G . West Nile virus: where are we now?. Lancet Infect Dis. 2004; 4(9):547-56. DOI: 10.1016/S1473-3099(04)01128-4. View

Yasui K . Protection of mice against Japanese encephalitis virus by passive administration with monoclonal antibodies. J Immunol. 1988; 141(10):3606-10. View

Meredith R, LoBuglio A, Plott W, ORR R, Brezovich I, Russell C . Pharmacokinetics, immune response, and biodistribution of iodine-131-labeled chimeric mouse/human IgG1,k 17-1A monoclonal antibody. J Nucl Med. 1991; 32(6):1162-8. View

Zhang W, Chipman P, Corver J, Johnson P, Zhang Y, Mukhopadhyay S . Visualization of membrane protein domains by cryo-electron microscopy of dengue virus. Nat Struct Biol. 2003; 10(11):907-12. PMC: 4148076. DOI: 10.1038/nsb990. View

Hieter P, Maizel Jr J, Leder P . Evolution of human immunoglobulin kappa J region genes. J Biol Chem. 1982; 257(3):1516-22. View

Klobeck H, Meindl A, Combriato G, Solomon A, Zachau H . Human immunoglobulin kappa light chain genes of subgroups II and III. Nucleic Acids Res. 1985; 13(18):6499-513. PMC: 321973. DOI: 10.1093/nar/13.18.6499. View

Modis Y, Ogata S, Clements D, Harrison S . A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A. 2003; 100(12):6986-91. PMC: 165817. DOI: 10.1073/pnas.0832193100. View

Diamond M, Shrestha B, Mehlhop E, Sitati E, Engle M . Innate and adaptive immune responses determine protection against disseminated infection by West Nile encephalitis virus. Viral Immunol. 2003; 16(3):259-78. DOI: 10.1089/088282403322396082. View

Modis Y, Ogata S, Clements D, Harrison S . Structure of the dengue virus envelope protein after membrane fusion. Nature. 2004; 427(6972):313-9. DOI: 10.1038/nature02165. View

10.

Chambers T, Halevy M, Nestorowicz A, Rice C, Lustig S . West Nile virus envelope proteins: nucleotide sequence analysis of strains differing in mouse neuroinvasiveness. J Gen Virol. 1998; 79 ( Pt 10):2375-80. DOI: 10.1099/0022-1317-79-10-2375. View

11.

Rey F, Heinz F, Mandl C, Kunz C, Harrison S . The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature. 1995; 375(6529):291-8. DOI: 10.1038/375291a0. View

12.

Mukhopadhyay S, Kim B, Chipman P, Rossmann M, Kuhn R . Structure of West Nile virus. Science. 2003; 302(5643):248. DOI: 10.1126/science.1089316. View

13.

Virgin 4th H, Bassel-Duby R, Fields B, Tyler K . Antibody protects against lethal infection with the neurally spreading reovirus type 3 (Dearing). J Virol. 1988; 62(12):4594-604. PMC: 253571. DOI: 10.1128/JVI.62.12.4594-4604.1988. View

14.

Tao M, Morrison S . Studies of aglycosylated chimeric mouse-human IgG. Role of carbohydrate in the structure and effector functions mediated by the human IgG constant region. J Immunol. 1989; 143(8):2595-601. View

15.

Chu J, Rajamanonmani R, Li J, Bhuvanakantham R, Lescar J, Ng M . Inhibition of West Nile virus entry by using a recombinant domain III from the envelope glycoprotein. J Gen Virol. 2005; 86(Pt 2):405-412. DOI: 10.1099/vir.0.80411-0. View

16.

Rey F . Dengue virus envelope glycoprotein structure: new insight into its interactions during viral entry. Proc Natl Acad Sci U S A. 2003; 100(12):6899-901. PMC: 165800. DOI: 10.1073/pnas.1332695100. View

17.

Diamond M, Roberts T, Edgil D, Lu B, Ernst J, Harris E . Modulation of Dengue virus infection in human cells by alpha, beta, and gamma interferons. J Virol. 2000; 74(11):4957-66. PMC: 110847. DOI: 10.1128/jvi.74.11.4957-4966.2000. View

18.

Wu K, Wu C, Tsao Y, Kuo T, Lou Y, Lin C . Structural basis of a flavivirus recognized by its neutralizing antibody: solution structure of the domain III of the Japanese encephalitis virus envelope protein. J Biol Chem. 2003; 278(46):46007-13. DOI: 10.1074/jbc.M307776200. View

19.

Beasley D, Aaskov J . Epitopes on the dengue 1 virus envelope protein recognized by neutralizing IgM monoclonal antibodies. Virology. 2001; 279(2):447-58. DOI: 10.1006/viro.2000.0721. View

20.

Wu S, Lian W, Hsu L, Liau M . Japanese encephalitis virus antigenic variants with characteristic differences in neutralization resistance and mouse virulence. Virus Res. 1998; 51(2):173-81. DOI: 10.1016/s0168-1702(97)00098-1. View