Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea
2006 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, Vol. 194, no 11, 1580-1588 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2006. Vol. 194, no 11, 1580-1588 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-35933Local ID: 29093OAI: oai:DiVA.org:liu-35933DiVA: diva2:256781