BOOSTING WITH RECOMBINANT VACCINIA INCREASES IMMUNOGENICITY AND PROTECTIVE EFFICACY OF MALARIA DNA VACCINE

To enhance the efficacy of DNA malaria vaccines, we evaluated the effe ct on protection of immunizing with various combinations of DNA, recom binant vaccinia virus, and a synthetic peptide. Immunization of BALB/c mice with a plasmid expressing Plasmodium yoelii (Py) circumsporozoit e protein (CSP) induces H-2K(d)-restricted CD8+ cytoxic T lymphocyte ( CTL) responses and CD8+ T cell- and interferon (IFN)-gamma-dependent p rotection of mice against challenge with Py sporozoites. Immunization with a multiple antigenic peptide, including the only reported H-2K(d) -restricted CD8+ T cell epitope on the PyCSP (PyCSP CTL multiple antig enic peptide) and immunization with recombinant vaccinia expressing th e PyCSP induced CTL but only modest to minimal protection, Mice were i mmunized with PyCSP DNA, PyCSP CTL multiple antigenic peptide, or reco mbinant vaccinia expressing PyCSP, were boosted 9 wk later with the sa me immunogen or one of the others, and were challenged, Only mice immu nized with DNA and boosted with vaccinia PyCSP (D-V) (11/16: 69%) or D NA (D-D) (7/16: 44%) had greater protection (P < 0.0007) than controls . D-V mice had significantly higher individual levels of antibodies an d class I-restricted CTL activity than did D-D mice; IFN-gamma product ion by ELIspot also was higher in D-V than in D-D mice. In a second ex periment. three different groups of D-V mice each had higher levels of protection than did D-D mice, and IFN-gamma production was significan tly greater in D-V than in D-D mice. The observation that priming with pyCSP DNA and boosting with vaccinia-PyCSP is more immunogenic and pr otective than immunizing with PyCSP DNA alone supports consideration o f a similar sequential immunization approach in humans.