Production of two vaccinating recombinant rotavirus proteins in the milk of transgenic rabbits

Rotaviruses are the main cause of infantile viral gastroenteritis worldwide leading to approximately 500,000 deaths each year mostly in the developing world. For unknown reasons, live attenuated viruses used in classical vaccine strategies were shown to be responsible for intussusception (a bowel ob...

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Bibliographic Details
Published in:Transgenic research 2005-12, Vol.14 (6), p.833-844
Main Authors: Soler, Eric, Le Saux, Agnès, Guinut, Frédéric, Passet, Bruno, Cohen, Ruxandra, Merle, Christine, Charpilienne, Annie, Fourgeux, Cynthia, Sorel, Véronique, Piriou, Antoine, Schwartz-Cornil, Isabelle, Cohen, Jean, Houdebine, Louis-Marie
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Animals, Genetically Modified
Antigens, Viral - biosynthesis
Antigens, Viral - genetics
Antigens, Viral - immunology
Capsid Proteins - biosynthesis
Capsid Proteins - genetics
Enzyme-Linked Immunosorbent Assay
Female
Genetics
Life Sciences
Medical research
Mice
Mice, Inbred BALB C
Milk
Milk - metabolism
Molecular Sequence Data
Rabbits - genetics
Recombinant Proteins - biosynthesis
Recombinant Proteins - genetics
Rotavirus
Rotavirus - immunology
Rotavirus Infections - immunology
Rotavirus Infections - prevention & control
Rotavirus Infections - virology
Rotavirus Vaccines - genetics
Rotavirus Vaccines - immunology
Vaccination
Vaccines, Synthetic - biosynthesis
Vaccines, Synthetic - genetics
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Summary:Rotaviruses are the main cause of infantile viral gastroenteritis worldwide leading to approximately 500,000 deaths each year mostly in the developing world. For unknown reasons, live attenuated viruses used in classical vaccine strategies were shown to be responsible for intussusception (a bowel obstruction). New strategies allowing production of safe recombinant non-replicating rotavirus candidate vaccine are thus clearly needed. In this study we utilized transgenic rabbit milk as a source of rotavirus antigens. Individual transgenic rabbit lines were able to produce several hundreds of micrograms per ml of secreted recombinant VP2 and VP6 proteins in their milk. Viral proteins expressed in our model were immunogenic and were shown to induce a significant reduction in viral antigen shedding after challenge with virulent rotavirus in the adult mouse model. To our knowledge, this is the first report of transgenic mammal bioreactors allowing the rapid co-production of two recombinant viral proteins in milk to be used as a vaccine.
ISSN:0962-8819
1573-9368
DOI:10.1007/s11248-005-1771-0