title: DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge.
abstract: We have tested the efficacy of DNA immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further improve immunogenicity of the native proteins, we generated expression vectors producing fusion of the proteins Gag and Env to the secreted chemokine MCP3, targeting the viral proteins to the secretory pathway and to a beta-catenin (CATE) peptide, targeting the viral proteins to the intracellular degradation pathway. Macaques immunized with vectors expressing the MCP3-tagged fusion proteins developed stronger antibody responses. Following mucosal challenge with pathogenic SIVmac251, the vaccinated animals showed a statistically significant decrease in viral load (P = 0.010). Interestingly, macaques immunized with a combination of vectors expressing three forms of antigens (native protein and MCP3 and CATE fusion proteins) showed the strongest decrease in viral load (P = 0.0059). Postchallenge enzyme-linked immunospot values for Gag and Env as well as gag-specific T-helper responses correlated with control of viremia. Our data show that the combinations of DNA vaccines producing native and modified forms of antigens elicit more balanced immune responses able to significantly reduce viremia for a long period (8 months) following pathogenic challenge with SIVmac251.
authors.affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, Bldg. 535, Rm. 210, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.forename: Agneta
authors.initials: A
authors.lastname: von Gegerfelt
authors.forename: Patricia
authors.initials: P
authors.lastname: Roth
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.forename: Marjorie
authors.initials: M
authors.lastname: Robert-Guroff
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Phil
authors.initials: P
authors.lastname: Markham
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; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002460:Cell Line; D015488:HIV Antigens / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019444:Vaccines, DNA; D014766:Viremia / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015488:HIV Antigens; D019444:Vaccines, DNA