title: Influenza and vaccinia viruses expressing malaria CD8+ T and B cell epitopes. Comparison of their immunogenicity and capacity to induce protective immunity.
abstract: We compared the effectiveness of several recombinant influenza and vaccinia viruses to induce a malaria-specific immune response. The CD8+ T cell epitope of the circumsporozoite (CS) protein of Plasmodium yoelii, a rodent malaria parasite, was expressed in two distinct influenza virus proteins, the hemagglutinin and the neuraminidase. These recombinant viruses were found to be equally efficient at inducing CS-specific CD8+ T cells in mice. A third recombinant virus, which expresses a B cell epitope of the CS protein, induced neutralizing anti-sporozoite Abs. Expression in the same recombinant virus of the CD8+ T cell epitope and of the B cell epitope did not impair the capacity of this recombinant virus to induce malaria-specific CD8+ T cells and neutralizing Abs. The immunogenicity of a vaccinia virus, expressing the entire CS protein, was compared with that of a highly attenuated vaccinia strain expressing the same protein and with that of another vaccinia virus expressing only the CD8+ T cell epitope. All three vaccinia virus recombinants elicited CS-specific CD8+ cells and a potent inhibitory response against pre-erythrocytic stages of malaria parasites. Optimal levels of anti-sporozoite Abs, inhibition of liver stage development, and protection against malaria infection resulted from repeatedly immunizing the animals with recombinant influenza viruses followed by boosters with a recombinant vaccinia virus. These findings support the concept that live viral vectors expressing the appropriate proteins and/or epitopes can be used as promising vaccine candidates.
authors.affiliation: Department of Medical and Molecular Parasitology, New York University School of Medicine 10010.
authors.forename: M
authors.initials: M
authors.lastname: Rodrigues
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: D
authors.initials: D
authors.lastname: Rodriguez
authors.forename: J R
authors.initials: JR
authors.lastname: Rodriguez
authors.forename: I
authors.initials: I
authors.lastname: Bacik
authors.forename: J R
authors.initials: JR
authors.lastname: Bennink
authors.forename: J W
authors.initials: JW
authors.lastname: Yewdell
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Sastre
authors.forename: R S
authors.initials: RS
authors.lastname: Nussenzweig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000235:genetics*; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C041595:circumsporozoite protein, Protozoan