Lactobacilli expressing variable domain of llama heavy-chain antibody fragments (lactobodies) confer protection against rotavirus-induced diarrhea.

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.

• Authors: Neha Pant, Anna Hultberg, Yaofeng Zhao, Lennart Svensson, Qiang Pan-Hammarstrom, Kari Johansen, Peter H Pouwels, Franco M Ruggeri, Pim Hermans, Leon Frenken, Thomas Boren, Harold Marcotte, Lennart Hammarstrom
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 194 Issue 11 Pg. 1580-8 (Dec 01 2006) ISSN: 0022-1899 [Print] United States
• PMID: 17083044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• Immunoglobulin Heavy Chains
• Immunoglobulin Variable Region

Topics

• Animals
• Antibodies, Viral (biosynthesis, genetics, immunology)
• Camelids, New World (immunology)
• Diarrhea (prevention & control)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Feces (virology)
• Genetic Vectors
• Immunization, Passive (methods)
• Immunoglobulin Heavy Chains (biosynthesis, genetics, immunology)
• Immunoglobulin Variable Region (biosynthesis, genetics, immunology)
• Lactobacillus (genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Microscopy, Electron, Scanning
• Protein Binding
• Rotavirus (immunology)
• Rotavirus Infections (prevention & control)