title: A new multi-clade DNA prime/recombinant MVA boost vaccine induces broad and high levels of HIV-1-specific CD8(+) T-cell and humoral responses in mice.
abstract: The results presented here are from the preclinical evaluation in BALB/c mice of a DNA prime/modified vaccinia virus Ankara (MVA) boost multi-gene multi-subtype human immunodeficiency virus-1 (HIV-1) vaccine intended for use in humans. The plasmid DNA vaccine was delivered intradermally using a Biojector, and the MVA was delivered intramuscularly by needle. This combination of recombinant DNA and MVA proved to induce extraordinarily strong cellular responses, with more than 80% of the CD8(+) T cells specific for HIV-1 antigens. Furthermore, we show that the DNA priming increases the number of T-cell epitopes recognized after the MVA boost. In the prime/boost-immunized animals, a significant proportion of CD8(+) T cells were stained positive for both interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), a feature that has been associated with control of HIV-1 infection in long-term non-progressors. The HIV-1-specific antibody levels were moderate after the plasmid DNA immunizations but increased dramatically after the MVA boost. Although the initial injection of MVA induced significant levels of vaccinia-neutralizing antibodies, the HIV-specific responses were still significantly boosted by the second MVA immunization. The results from this study demonstrate the potency of this combination of DNA plasmids and MVA construct to induce broad and high levels of immune responses against several HIV-1 proteins of different subtypes.
authors.affiliation: Swedish Institute for Infectious Disease Control, Solna, Sweden. andreas.brave@smi.ki.se
authors.forename: Andreas
authors.initials: A
authors.lastname: Bråve
authors.forename: Andreas
authors.initials: A
authors.lastname: Boberg
authors.forename: Lindvi
authors.initials: L
authors.lastname: Gudmundsdotter
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Kristian
authors.initials: K
authors.lastname: Hallermalm
authors.forename: Karl
authors.initials: K
authors.lastname: Ljungberg
authors.forename: Pontus
authors.initials: P
authors.lastname: Blomberg
authors.forename: Richard
authors.initials: R
authors.lastname: Stout
authors.forename: Staffan
authors.initials: S
authors.lastname: Paulie
authors.forename: Eric
authors.initials: E
authors.lastname: Sandström
authors.forename: Gunnel
authors.initials: G
authors.lastname: Biberfeld
authors.forename: Patricia
authors.initials: P
authors.lastname: Earl
authors.forename: Bernard
authors.initials: B
authors.lastname: Moss
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Cox
authors.forename: Britta
authors.initials: B
authors.lastname: Wahren
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
chemical_list: D019302:HIV Envelope Protein gp160; D007376:Interleukin-2; D019444:Vaccines, DNA; D007371:Interferon-gamma