Journal Article

Lactobacilli Expressing Variable Domain of Llama Heavy-Chain Antibody Fragments (Lactobodies) Confer Protection against Rotavirus-Induced Diarrhea

Svensson, Lennart, Pan-Hammarström, Qiang, Johansen, Kari, Borén, Thomas, Pant, Neha, Zhao, Yaofeng, Hultberg, Anna, Pouwels, Peter H., Hermans, Pim, Ruggeri, Franco M., Frenken, Leon, Marcotte, Harold, Hammarström, Lennart

2006

Overview

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

• Publisher: The University of Chicago Press,University of Chicago Press
• Subject: Animals / Antibodies / Antibodies, Viral - biosynthesis / Antibodies, Viral - genetics / Antibodies, Viral - immunology / Biological and medical sciences / Camelids, New World - immunology / Diarrhea / Diarrhea - prevention & control / Disease Models, Animal / Dosage / Enzyme-Linked Immunosorbent Assay / Feces - virology / Fundamental and applied biological sciences. Psychology / Genes / Genetic Vectors / Immunization, Passive - methods / Immunoglobulin fragments / Immunoglobulin Heavy Chains - biosynthesis / Immunoglobulin Heavy Chains - genetics / Immunoglobulin Heavy Chains - immunology / Immunoglobulin Heavy Chains/biosynthesis/genetics/immunology / Immunoglobulin Variable Region - biosynthesis / Immunoglobulin Variable Region - genetics / Immunoglobulin Variable Region - immunology / Immunoglobulin Variable Region/biosynthesis/genetics/immunology / Infections / Infectious diseases / Lactobacillus / Lactobacillus - genetics / Lactobacillus - immunology / Lactobacillus paracasei / Lactobacillus/genetics/immunology / Medical sciences / MEDICIN / MEDICINE / Mice / Mice, Inbred BALB C / Microbiology / Microscopy, Electron, Scanning / Miscellaneous / Protein Binding / Rotavirus / Rotavirus - immunology / Rotavirus infections / Rotavirus Infections - prevention & control / Virology / Viruses