Engineering poliovirus as a vaccine vector for the expression of diverse antigens.
As a step toward developing poliovirus as a vaccine vector, poliovirus recombinants were constructed by fusing exogenous peptides (up to 400 amino acids) and an artificial cleavage site for viral protease 3Cpro to the amino terminus of the viral polyprotein. Viral replication proceeded normally. An extended polyprotein was produced in infected cells and proteolytically processed into the complete array of viral proteins plus the foreign peptide, which was excluded from mature virions. The recombinants retained exogenous sequences through successive rounds of replication in culture and in vivo. Infection of animals with recombinants elicited a humoral immune response to the foreign peptides.
Andino
R
R
Department of Microbiology and Immunology, University of California, San Francisco.
Silvera
D
D
Suggett
S D
SD
Achacoso
P L
PL
Miller
C J
CJ
Baltimore
D
D
Feinberg
M B
MB
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D005818:Genetic Engineering; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D011055:Poliovirus Vaccine, Oral / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D000942:Antigens, Bacterial; D000956:Antigens, Viral; D011055:Poliovirus Vaccine, Oral; D011506:Proteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic