Print Email Facebook Twitter Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea Title Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea Author Pant, N. Hultberg, A. Zhao, Y. Svensson, L. Pan-Hammarström, Q. Johansen, K. Pouwels, P.H. Ruggeri, F.M. Hermans, P. Frenken, L. Borén, T. Marcotte, H. Hammarström, L. TNO Preventie en Gezondheid Publication year 2006 Abstract Background. Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and mortality among children in developing countries. We therefore developed a system for passive immunotherapy in which recombinant lactobacilli constitutively express neutralizing variable domain of llama heavy-chain (VHH) antibody fragments against rotavirus. Methods. VHH were expressed in Lactobacillus paracasei, in both secreted and cell surface-anchored forms. Electron microscopy was used to investigate the binding efficacy of VHH-expressing lactobacilli. To investigate the in vivo function of VHH-expressing lactobacilli, a mouse pup model of rotavirus infection was used. Results. Efficient binding of the VHH antibody fragments to rotavirus was shown by enzyme-linked immunosorbent assay and scanning electron microscopy. VHH fragments expressed by lactobacilli conferred a significant reduction in infection in cell cultures. When administered orally, lactobacilli-producing surface-expressed VHH markedly shortened disease duration, severity, and viral load in a mouse model of rotavirus-induced diarrhea when administered both fresh and in a freeze-dried form. Conclusions. Transformed lactobacilli may form the basis of a novel form of prophylactic treatment against rotavirus infections and other diarrheal diseases. © 2006 by the Infectious Diseases Society of America. All rights reserved. Chemicals / CAS: Antibodies, Viral; Immunoglobulin Heavy Chains; Immunoglobulin Variable Region Subject BiologyAntibodyImmunoglobulin heavy chainAnimal experimentAnimal modelAnimal tissueArtiodactylaBinding affinityCell cultureControlled studyDisease durationDisease severityElectron microscopyEnzyme linked immunosorbent assayImmunityInfectious diarrheaLactobacillus paracaseiLamaMouseNonhumanNucleotide sequenceScanning electron microscopeVirus loadVirus neutralizationAnimalsAntibodies, ViralCamelids, New WorldDiarrheaDisease Models, AnimalEnzyme-Linked Immunosorbent AssayFecesGenetic VectorsImmunization, PassiveImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionLactobacillusMiceMice, Inbred BALB CMicroscopy, Electron, ScanningProtein BindingRotavirusRotavirus Infections To reference this document use: http://resolver.tudelft.nl/uuid:83adec60-c7c9-4ac8-9ea1-66dbeb3725b4 DOI https://doi.org/10.1086/508747 TNO identifier 239669 ISSN 0022-1899 Source Journal of Infectious Diseases, 194 (11), 1580-1588 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.