PRIMING WITH RECOMBINANT INFLUENZA-VIRUS FOLLOWED BY ADMINISTRATION OF RECOMBINANT VACCINIA VIRUS INDUCES CD8-CELL-MEDIATED PROTECTIVE IMMUNITY AGAINST MALARIA( T)

Live vectors expressing foreign antigens have been used to induce immu nity against several pathogens. However, for the virulent rodent malar ia parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite pro tein of this parasite, failed to induce protection. We generated a rec ombinant influenza virus expressing an epitope from the circumsporozoi te protein of P. yoelii known to be recognized by CD8+ T cells and dem onstrated that this vector induced class I major histocompatibility co mplex-restricted cytotoxic T cells against this foreign epitope. Immun ization of mice with this recombinant influenza virus, followed by a r ecombinant vaccinia virus expressing the entire circumsporozoite prote in, induced protective immunity against sporozoite-induced malaria. Th e sequence of immunization appears to be crucial, since a primer injec tion with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The pro tection induced by immunization with these recombinant viruses is most ly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monocl onal antibody abolishes the anti-malarial immunity. The use of differe nt live vectors for primer and booster injections has a synergistic ef fect on the immune response and might represent an effective general s trategy for eliciting protective immune responses to key antigens of m icrobial pathogens.