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Journal of Virology, October 2008, p. 9753-9764, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00436-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Llama-Derived Single-Chain Antibody Fragments Directed to Rotavirus VP6 Protein Possess Broad Neutralizing Activity In Vitro and Confer Protection against Diarrhea in Mice{triangledown}

Lorena Garaicoechea,1*,{dagger} Aurelien Olichon,2,{dagger} Gisela Marcoppido,1 Andrés Wigdorovitz,1 Marina Mozgovoj,1 Linda Saif,3 Thomas Surrey,2 and Viviana Parreño1

Instituto de Virología, CICV y A-INTA, Buenos Aires, Argentina,1 European Molecular Biology Laboratory, Cell Biology and Biophysics Unit, Meyerhofstr. 1, 69117 Heidelberg, Germany,2 Food Animal Health Research Program, Department of Veterinary Preventive Medicine, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio 44691-409613

Received 27 February 2008/ Accepted 7 July 2008

Group A rotavirus is one of the most common causes of severe diarrhea in human infants and newborn animals. Rotavirus virions are triple-layered particles. The outer capsid proteins VP4 and VP7 are highly variable and represent the major neutralizing antigens. The inner capsid protein VP6 is conserved among group A rotaviruses, is highly immunogenic, and is the target antigen of most immunodiagnosis tests. Llama-derived single-chain antibody fragments (VHH) are the smallest molecules with antigen-binding capacity and can therefore be expected to have properties different from conventional antibodies. In this study a library containing the VHH genes of a llama immunized with recombinant inner capsid protein VP6 was generated. Binders directed to VP6, in its native conformation within the viral particle, were selected and characterized. Four selected VHH directed to conformational epitopes of VP6 recognized all human and animal rotavirus strains tested and could be engineered for their use in immunodiagnostic tests for group A rotavirus detection. Three of the four VHH neutralized rotavirus in vivo independently of the strain serotype. Furthermore, this result was confirmed by in vivo partial protection against rotavirus challenge in a neonatal mouse model. The present study demonstrates for the first time a broad neutralization activity of VP6 specific VHH in vitro and in vivo. Neutralizing VHH directed to VP6 promise to become an essential tool for the prevention and treatment of rotavirus diarrhea.

* Corresponding author. Mailing address: Instituto de Virología, CICV y A-INTA, CC 25 (1712) Castelar, Buenos Aires, Argentina. Phone: 54 11 4621 9050. Fax: 54 11 4621 9050. E-mail: lgaraicoechea{at}cnia.inta.gov.ar

{triangledown} Published ahead of print on 16 July 2008.

{dagger} L.G. and A.O. contributed equally to this study.

Journal of Virology, October 2008, p. 9753-9764, Vol. 82, No. 19
0022-538X/08/$08.00+0     doi:10.1128/JVI.00436-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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