Skip to main content
Top
Published in: Virology Journal 1/2009

Open Access 01-12-2009 | Research

Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

Authors: Lyn M O'Brien, Cindy D Underwood-Fowler, Sarah A Goodchild, Amanda L Phelps, Robert J Phillpotts

Published in: Virology Journal | Issue 1/2009

Login to get access

Abstract

Background

There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology.

Results

In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv) isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge.

Conclusion

A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans.
Crown Copyright © 2009
Appendix
Available only for authorised users
Literature
1.
go back to reference Weaver SC, Ferro C, Barrera R, Boshell J, Navarro JC: Venezuelan equine encephalitis. Annu Rev Entomol 2004, 49: 141-174. 10.1146/annurev.ento.49.061802.123422CrossRefPubMed Weaver SC, Ferro C, Barrera R, Boshell J, Navarro JC: Venezuelan equine encephalitis. Annu Rev Entomol 2004, 49: 141-174. 10.1146/annurev.ento.49.061802.123422CrossRefPubMed
2.
go back to reference Johnson KM, Martin DH: Venezuelan equine encephalitis. Adv Vet Sci Comp Med 1974, 18: 79-116.PubMed Johnson KM, Martin DH: Venezuelan equine encephalitis. Adv Vet Sci Comp Med 1974, 18: 79-116.PubMed
3.
go back to reference Pittman PR, Makuch RS, Mangiafico JA, Cannon TL, Gibbs PH, Peters CJ: Long-term duration of detectable neutralising antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine. Vaccine 1996, 14: 337-343. 10.1016/0264-410X(95)00168-ZCrossRefPubMed Pittman PR, Makuch RS, Mangiafico JA, Cannon TL, Gibbs PH, Peters CJ: Long-term duration of detectable neutralising antibodies after administration of live-attenuated VEE vaccine and following booster vaccination with inactivated VEE vaccine. Vaccine 1996, 14: 337-343. 10.1016/0264-410X(95)00168-ZCrossRefPubMed
4.
go back to reference Rayfield EJ, Gorelkin L, Kurnow RT, Jahrling PB: Virus-induced pancreatic disease by Venezuelan encephalitis virus. Alterations in glucose tolerance and insulin release. Diabetes 1976, 25: 623-631. 10.2337/diabetes.25.7.623CrossRefPubMed Rayfield EJ, Gorelkin L, Kurnow RT, Jahrling PB: Virus-induced pancreatic disease by Venezuelan encephalitis virus. Alterations in glucose tolerance and insulin release. Diabetes 1976, 25: 623-631. 10.2337/diabetes.25.7.623CrossRefPubMed
5.
go back to reference Casamassima AC, Hess LW, Marty A: TC-83 Venezuelan equine encephalitis vaccine exposure during pregnancy. Teratology 1987, 36: 287-289. 10.1002/tera.1420360303CrossRefPubMed Casamassima AC, Hess LW, Marty A: TC-83 Venezuelan equine encephalitis vaccine exposure during pregnancy. Teratology 1987, 36: 287-289. 10.1002/tera.1420360303CrossRefPubMed
6.
go back to reference Ni H, Yun NE, Zacks MA, Weaver SC, Tesh RB, Travassos Da Rosa AP, Powers AM, Frolov I, Paessler S: Recombinant alphaviruses are safe and useful serological diagnostic tools. Am J Trop Med Hyg 2007, 76: 774-781.PubMed Ni H, Yun NE, Zacks MA, Weaver SC, Tesh RB, Travassos Da Rosa AP, Powers AM, Frolov I, Paessler S: Recombinant alphaviruses are safe and useful serological diagnostic tools. Am J Trop Med Hyg 2007, 76: 774-781.PubMed
7.
go back to reference The Subcommitee on Arbovirus Laboratory Safety of the American Committee on Arthropod-borne Viruses: Laboratory safety for Arbovirus and certain other viruses of vertebrates. Am J Trop Med Hyg 1980, 29: 1359-1381. The Subcommitee on Arbovirus Laboratory Safety of the American Committee on Arthropod-borne Viruses: Laboratory safety for Arbovirus and certain other viruses of vertebrates. Am J Trop Med Hyg 1980, 29: 1359-1381.
8.
go back to reference Phillpotts RJ, Jones LD, Howard SC: Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus. Vaccine 2002, 20: 1497-1504. 10.1016/S0264-410X(01)00505-9CrossRefPubMed Phillpotts RJ, Jones LD, Howard SC: Monoclonal antibody protects mice against infection and disease when given either before or up to 24 h after airborne challenge with virulent Venezuelan equine encephalitis virus. Vaccine 2002, 20: 1497-1504. 10.1016/S0264-410X(01)00505-9CrossRefPubMed
9.
go back to reference Hunt AR, Frederickson S, Hinkel C, Bowdish KS, Roehrig JT: A humanised murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus. J Gen Virol 2006, 87: 2467-2476. 10.1099/vir.0.81925-0CrossRefPubMed Hunt AR, Frederickson S, Hinkel C, Bowdish KS, Roehrig JT: A humanised murine monoclonal antibody protects mice either before or after challenge with virulent Venezuelan equine encephalomyelitis virus. J Gen Virol 2006, 87: 2467-2476. 10.1099/vir.0.81925-0CrossRefPubMed
10.
go back to reference Phillpotts RJ: Venezuelan equine encephalitis virus complex-specific monoclonal antibody provides broad protection, in murine models, against airborne challenge with viruses from serogroups I, II and III. Virus Res 2006, 120: 107-112. 10.1016/j.virusres.2006.02.003CrossRefPubMed Phillpotts RJ: Venezuelan equine encephalitis virus complex-specific monoclonal antibody provides broad protection, in murine models, against airborne challenge with viruses from serogroups I, II and III. Virus Res 2006, 120: 107-112. 10.1016/j.virusres.2006.02.003CrossRefPubMed
11.
go back to reference Mathews JH, Roehrig JT, Trent DW: Role of complement and the Fc portion of immunoglobulin G in immunity to Venezuelan equine encephalomyelitis virus infection with glycoprotein-specific monoclonal antibodies. J Virol 1985, 55: 594-600.PubMedCentralPubMed Mathews JH, Roehrig JT, Trent DW: Role of complement and the Fc portion of immunoglobulin G in immunity to Venezuelan equine encephalomyelitis virus infection with glycoprotein-specific monoclonal antibodies. J Virol 1985, 55: 594-600.PubMedCentralPubMed
12.
go back to reference Marasco WA, Sui J: The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 2007, 25: 1421-1434. 10.1038/nbt1363CrossRefPubMed Marasco WA, Sui J: The growth and potential of human antiviral monoclonal antibody therapeutics. Nat Biotechnol 2007, 25: 1421-1434. 10.1038/nbt1363CrossRefPubMed
13.
go back to reference Kirsch MI, Hülseweh B, Nacke C, Rülker T, Schirrmann T, Marschall HJ, Hurst M, Dübel S: Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV). BMC Biotechnol 2008, 8: 66. 10.1186/1472-6750-8-66PubMedCentralCrossRefPubMed Kirsch MI, Hülseweh B, Nacke C, Rülker T, Schirrmann T, Marschall HJ, Hurst M, Dübel S: Development of human antibody fragments using antibody phage display for the detection and diagnosis of Venezuelan equine encephalitis virus (VEEV). BMC Biotechnol 2008, 8: 66. 10.1186/1472-6750-8-66PubMedCentralCrossRefPubMed
14.
go back to reference Bennett AM, Elvin SJ, Wright AJ, Jones SM, Phillpotts RJ: An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine. Vaccine 2001, 19: 337-347. 10.1016/S0264-410X(00)00123-7CrossRef Bennett AM, Elvin SJ, Wright AJ, Jones SM, Phillpotts RJ: An immunological profile of Balb/c mice protected from airborne challenge following vaccination with a live attenuated Venezuelan equine encephalitis virus vaccine. Vaccine 2001, 19: 337-347. 10.1016/S0264-410X(00)00123-7CrossRef
15.
go back to reference Phillpotts RJ, O'Brien L, Appleton RE, Carr S, Bennett A: Intranasal immunisation with defective Adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus. Vaccine 2005, 23: 1615-1623. 10.1016/j.vaccine.2004.06.056CrossRefPubMed Phillpotts RJ, O'Brien L, Appleton RE, Carr S, Bennett A: Intranasal immunisation with defective Adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus. Vaccine 2005, 23: 1615-1623. 10.1016/j.vaccine.2004.06.056CrossRefPubMed
16.
go back to reference Burmester J, Plückthun A: Construction of scFv fragments from Hybridoma or Spleen cells by PCR assembly. In Antibody Engineering. Edited by: Kontermann R, Dübel S. Springer-Verlag; 2001:19-40.CrossRef Burmester J, Plückthun A: Construction of scFv fragments from Hybridoma or Spleen cells by PCR assembly. In Antibody Engineering. Edited by: Kontermann R, Dübel S. Springer-Verlag; 2001:19-40.CrossRef
17.
go back to reference Krebber A, Bornhauser S, Burmester J, Honegger A, Willuda J, Bosshard HR, Plückthun A: Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a re-engineered phage display system. J Immunol Methods 1997, 201: 35-55. 10.1016/S0022-1759(96)00208-6CrossRefPubMed Krebber A, Bornhauser S, Burmester J, Honegger A, Willuda J, Bosshard HR, Plückthun A: Reliable cloning of functional antibody variable domains from hybridomas and spleen cell repertoires employing a re-engineered phage display system. J Immunol Methods 1997, 201: 35-55. 10.1016/S0022-1759(96)00208-6CrossRefPubMed
18.
19.
go back to reference Wright AJ, Phillpotts RJ: Humane endpoints are an objective measure of morbidity in Venezuelan encephalomyelitis virus infection of mice. Arch Virol 1998, 143: 1155-1162. 10.1007/s007050050363CrossRefPubMed Wright AJ, Phillpotts RJ: Humane endpoints are an objective measure of morbidity in Venezuelan encephalomyelitis virus infection of mice. Arch Virol 1998, 143: 1155-1162. 10.1007/s007050050363CrossRefPubMed
20.
go back to reference Butcher W, Ulaeto D: Contact inhibition of Orthopoxviruses by household disinfectants. J Appl Microbiol 2005, 99: 279-284. 10.1111/j.1365-2672.2005.02601.xCrossRefPubMed Butcher W, Ulaeto D: Contact inhibition of Orthopoxviruses by household disinfectants. J Appl Microbiol 2005, 99: 279-284. 10.1111/j.1365-2672.2005.02601.xCrossRefPubMed
21.
go back to reference Dubois E, Merle G, Roquier C, Trompette A, Le Guyader F, Crucière C, Chomel J-J: Diversity of enterovirus sequences detected in oysters by RT-heminested PCR. Int J Food Microbiol 2004, 92: 35-43. 10.1016/j.ijfoodmicro.2003.06.001CrossRefPubMed Dubois E, Merle G, Roquier C, Trompette A, Le Guyader F, Crucière C, Chomel J-J: Diversity of enterovirus sequences detected in oysters by RT-heminested PCR. Int J Food Microbiol 2004, 92: 35-43. 10.1016/j.ijfoodmicro.2003.06.001CrossRefPubMed
Metadata
Title
Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains
Authors
Lyn M O'Brien
Cindy D Underwood-Fowler
Sarah A Goodchild
Amanda L Phelps
Robert J Phillpotts
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2009
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/1743-422X-6-206

Other articles of this Issue 1/2009

Virology Journal 1/2009 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine