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 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.
Soler
Eric
E
Biologie du Développement et de la Reproduction, INRA, bât.440, Jouy-en-Josas, France. eric.soler@jouy.inra.fr
Le Saux
Agnès
A
Guinut
Frédéric
F
Passet
Bruno
B
Cohen
Ruxandra
R
Merle
Christine
C
Charpilienne
Annie
A
Fourgeux
Cynthia
C
Sorel
Véronique
V
Piriou
Antoine
A
Schwartz-Cornil
Isabelle
I
Cohen
Jean
J
Houdebine
Louis-Marie
LM
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000956:Antigens, Viral / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000378:metabolism*; D008969:Molecular Sequence Data; D011817:Rabbits / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D022243:Rotavirus Vaccines / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000235:genetics
D000956:Antigens, Viral; D036022:Capsid Proteins; D011994:Recombinant Proteins; D022243:Rotavirus Vaccines; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic