title: Improvement of antibody responses by HIV envelope DNA and protein co-immunization.
abstract: BACKGROUND
  Developing HIV envelope (Env) vaccine components that elicit durable and protective antibody responses is an urgent priority, given the results from the RV144 trial. Optimization of both the immunogens and vaccination strategies will be needed to generate potent, durable antibodies. Due to the diversity of HIV, an effective Env-based vaccine will most likely require an extensive coverage of antigenic variants. A vaccine co-delivering Env immunogens as DNA and protein components could provide such coverage. Here, we examine a DNA and protein co-immunization strategy by characterizing the antibody responses and evaluating the relative contribution of each vaccine component.
  
  
  METHODS
  We co-immunized rabbits with representative subtype A or B HIV gp160 plasmid DNA plus Env gp140 trimeric glycoprotein and compared the responses to those obtained with either glycoprotein alone or glycoprotein in combination with empty vector.
  
  
  RESULTS
  DNA and glycoprotein co-immunization was superior to immunization with glycoprotein alone by enhancing antibody kinetics, magnitude, avidity, and neutralizing potency. Importantly, the empty DNA vector did not contribute to these responses. Humoral responses elicited by mismatched DNA and protein components were comparable or higher than the responses produced by the matched vaccines.
  
  
  CONCLUSIONS
  Our data show that co-delivering DNA and protein can augment antibodies to Env. The rate and magnitude of immune responses suggest that this approach has the potential to streamline vaccine regimens by inducing higher antibody responses using fewer vaccinations, an advantage for a successful HIV vaccine design.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97217, United States; The Vaccine and Gene Therapy Institute, Beaverton, OR 97006, United States; Oregon National Primate Research Center, Beaverton, OR 97006, United States.
authors.forename: Franco
authors.initials: F
authors.lastname: Pissani
authors.affiliation: Oregon National Primate Research Center, Beaverton, OR 97006, United States.
authors.forename: Delphine C
authors.initials: DC
authors.lastname: Malherbe
authors.affiliation: GE Healthcare, Life Sciences, Piscataway, NJ 08854, United States.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Schuman
authors.affiliation: Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States.
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
authors.affiliation: Oregon National Primate Research Center, Beaverton, OR 97006, United States; Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR 97239, United States.
authors.forename: Byung S
authors.initials: BS
authors.lastname: Park
authors.affiliation: The Vaccine and Gene Therapy Institute, Beaverton, OR 97006, United States; Oregon National Primate Research Center, Beaverton, OR 97006, United States.
authors.forename: Shelly J
authors.initials: SJ
authors.lastname: Krebs
authors.affiliation: Novartis Institutes for Biomedical Research, Cambridge, MA 02139, United States.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97217, United States; The Vaccine and Gene Therapy Institute, Beaverton, OR 97006, United States; Oregon National Primate Research Center, Beaverton, OR 97006, United States. Electronic address: haigwoon@ohsu.edu.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Haigwood
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000915:Antibody Affinity; D000917:Antibody Formation; D004279:DNA, Viral / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D019302:HIV Envelope Protein gp160 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D011817:Rabbits; D019444:Vaccines, DNA / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D004279:DNA, Viral; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1
keywords: DNA+protein co-immunization; Envelope-based vaccine; HIV; Neutralizing antibodies