title: Comparison of immune responses generated by optimized DNA vaccination against SIV antigens in mice and macaques.
abstract: Optimized DNA vectors were constructed comprising the proteome of SIV including the structural, enzymatic, regulatory, and accessory proteins. In addition to native antigens as produced by the virus, fusion proteins and modified antigens with altered secretion, cellular localization and stability characteristics were generated. The DNA vectors were tested for expression upon transfection in human cells. In addition, the vectors were tested either alone or in combinations in mice and macaques, which provided an opportunity to compare immune responses in two animal models. DNA only immunization using intramuscular injection in the absence or presence of in vivo electroporation did not alter the phenotype of the induced T cell responses in mice. Although several fusion proteins induced immune responses to all the components of a polyprotein, we noted fusion proteins that abrogated immune response to some of the components. Since the expression levels of such fusion proteins were not affected, these data suggest that the immune recognition of certain components was altered by the fusion. Testing different DNA vectors in mice and macaques revealed that a combination of DNAs producing different forms of the same antigen generated more balanced immune responses, a desirable feature for an optimal AIDS vaccine.
authors.affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.forename: Brunda
authors.initials: B
authors.lastname: Ganneru
authors.forename: Cristina
authors.initials: C
authors.lastname: Bergamaschi
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Agneta
authors.initials: A
authors.lastname: von Gegerfelt
authors.forename: Vainav
authors.initials: V
authors.lastname: Patel
authors.forename: Gen-Mu
authors.initials: GM
authors.lastname: Zhang
authors.forename: Bhabadeb
authors.initials: B
authors.lastname: Chowdhury
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D003001:Cloning, Molecular; D018274:Electroporation; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D011993:Recombinant Fusion Proteins; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma