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
Biology
Antibody
Immunoglobulin heavy chain
Animal experiment
Animal model
Animal tissue
Artiodactyla
Binding affinity
Cell culture
Controlled study
Disease duration
Disease severity
Electron microscopy
Enzyme linked immunosorbent assay
Immunity
Infectious diarrhea
Lactobacillus paracasei
Lama
Mouse
Nonhuman
Nucleotide sequence
Scanning electron microscope
Virus load
Virus neutralization
Animals
Antibodies, Viral
Camelids, New World
Diarrhea
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Feces
Genetic Vectors
Immunization, Passive
Immunoglobulin Heavy Chains
Immunoglobulin Variable Region
Lactobacillus
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Protein Binding
Rotavirus
Rotavirus Infections
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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