Nasal immunisation with Salmonella typhimurium producing rotavirus VP2 and VP6 antigens stimulates specific antibody response in serum and milk but fails to protect offspring.
Rotavirus specifically infects the small intestine of young infants resulting in severe diarrhoea. Mucosal antibody responses are required to cure the infection, and mucosal administration of rotavirus-like particles induces protective immunity without requiring a mucosal adjuvant such as cholera toxin. In addition, the rotavirus protein VP6 has been defined as a protective antigen in an adult mouse rotavirus infection model. Salmonella typhimurium is an epithelium-invasive bacterium that induces specific immune responses in mucosal tissues against itself and carried antigens. In this work, we investigated the capacity of a live recombinant S. typhimurium vaccine to stimulate antibody responses against rotavirus. We constructed an attenuated S. typhimurium strain simultaneously producing VP6 and VP2 rotavirus proteins in the cytoplasm. In contrast to expression in eukaryotic cells, VP6 and VP2 did not form virus-like particles in our bacterial system. After nasal administration of female mice, the live recombinant Salmonella were able to elicit an antibody response specific to both VP2 and VP6 in serum and milk. However, these antibodies failed to passively protect the offspring against rotavirus-induced diarrhoea.
Coste
A
A
Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland. acoste@clermont.inra.fr
Cohen
J
J
Reinhardt
M
M
Kraehenbuhl
J P
JP
Sirard
J C
JC
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral; D002213:Capsid / Q000276:immunology*; D036022:Capsid Proteins; D005260:Female; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000276:immunology*; D012401:Rotavirus / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D014614:Vaccines, Synthetic; D014765:Viral Vaccines