title: Boosting with recombinant vaccinia increases immunogenicity and protective efficacy of malaria DNA vaccine.
abstract: To enhance the efficacy of DNA malaria vaccines, we evaluated the effect on protection of immunizing with various combinations of DNA, recombinant vaccinia virus, and a synthetic peptide. Immunization of BALB/c mice with a plasmid expressing Plasmodium yoelii (Py) circumsporozoite protein (CSP) induces H-2Kd-restricted CD8+ cytotoxic T lymphocyte (CTL) responses and CD8+ T cell- and interferon (IFN)-gamma-dependent protection of mice against challenge with Py sporozoites. Immunization with a multiple antigenic peptide, including the only reported H-2Kd-restricted CD8+ T cell epitope on the PyCSP (PyCSP CTL multiple antigenic peptide) and immunization with recombinant vaccinia expressing the PyCSP induced CTL but only modest to minimal protection. Mice were immunized with PyCSP DNA, PyCSP CTL multiple antigenic peptide, or recombinant vaccinia expressing PyCSP, were boosted 9 wk later with the same immunogen or one of the others, and were challenged. Only mice immunized with DNA and boosted with vaccinia PyCSP (D-V) (11/16: 69%) or DNA (D-D) (7/16: 44%) had greater protection (P < 0. 0007) than controls. D-V mice had significantly higher individual levels of antibodies and class I-restricted CTL activity than did D-D mice; IFN-gamma production by ELIspot also was higher in D-V than in D-D mice. In a second experiment, three different groups of D-V mice each had higher levels of protection than did D-D mice, and IFN-gamma production was significantly 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 protective than immunizing with PyCSP DNA alone supports consideration of a similar sequential immunization approach in humans.
authors.affiliation: Malaria Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sedegah
authors.forename: T R
authors.initials: TR
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Kaur
authors.forename: R
authors.initials: R
authors.lastname: Hedstrom
authors.forename: P
authors.initials: P
authors.lastname: Hobart
authors.forename: J A
authors.initials: JA
authors.lastname: Tine
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007371:Interferon-gamma / Q000378:metabolism; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000627:therapeutic use; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma