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.
© 1994 American Association for the Advancement of Science. Received 24 March 1994; accepted 12 July 1994. We thank R. K. Taylor for antiserum to tcpA, J. Mekalanos for antiserum to CTB, M. Scott for monoclonal antibody to HA, V. R. Racaniello and A. Nomoto for the PVR-transgenic mice, and A. Frankel, K. Saksela, S. Staprans, and J. A. T. Young for comments on the manuscript. This work was initiated at the Whitehead Institute for Biomedical Research and was supported by PHS grant no. AI22346 (D.B.), NIH grant no. AI35545 (C.J.M.), the University of California at Davis grant no. RR00169 (C.J.M.), funds from the Gladstone Institute (R.A. and M.B.F.), and the AIDS Clinic Research Center at the University of California (M.B.F.).