Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea
N Pant, A Hultberg, Y Zhao, L Svensson… - The Journal of …, 2006 - academic.oup.com
N Pant, A Hultberg, Y Zhao, L Svensson, Q Pan-Hammarström, K Johansen, PH Pouwels…
The Journal of infectious diseases, 2006•academic.oup.comBackground 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 …
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 …
Abstract
BackgroundRotavirus-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
MethodsVHH 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
ResultsEfficient 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
ConclusionsTransformed lactobacilli may form the basis of a novel form of prophylactic treatment against rotavirus infections and other diarrheal diseases
Oxford University Press