Delivery and expression of a heterologous antigen on the surface of streptococci.
We have developed a system in which a foreign antigen replaces nearly all of the surface-exposed region of the fibrillar M protein from Streptococcus pyogenes and is fused to the C-terminal attachment motif of the M molecule. The fusion protein is thus expressed on the surface of Streptococcus gordonii, a commensal organism of the oral cavity. The antigen chosen to be expressed within the context of the M6 molecule was the E7 protein (98 amino acids) of human papillomavirus type 16. Stable recombinant streptococci were obtained by integrating genetic constructs into the chromosome, exploiting in vivo homologous recombination. The M6-E7 fusion protein expressed on the S. gordonii surface was shown to be immunogenic in mice. This is the first step in the construction of recombinant live vaccines in which nonpathogenic streptococci as well as other gram-positive bacteria may be used as vectors to deliver heterologous antigens to the immune system.
Pozzi
G
G
Dipartimento di Biologia Molecolare, Università di Siena, Italy.
Contorni
M
M
Oggioni
M R
MR
Manganelli
R
R
Tommasino
M
M
Cavalieri
F
F
Fischetti
V A
VA
D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002352:Carrier Proteins; D003001:Cloning, Molecular; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology; D013291:Streptococcus / Q000276:immunology*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D011993:Recombinant Fusion Proteins; C014689:streptococcal M protein