title: Antibody responses to prime-boost vaccination with an HIV-1 gp145 envelope protein and chimpanzee adenovirus vectors expressing HIV-1 gp140.
abstract: Over 2 million individuals are infected with HIV type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies with protection, thus providing a path toward a more effective vaccine. We sought to test the antibody response from novel prime-boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env glycoprotein (gp)140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate.
  
  
  
  Three different prime-boost regimens were tested in mice: AdC prime-protein boost, protein prime-AdC boost, and AdC prime-AdC boost. Each regimen was tested at two different doses of AdC vector in a total of six experimental groups.
  
  
  
  Sera were collected at various time points and evaluated by ELISA for Env-specific antibody binding, isotype, and avidity. Antibody functionality was assessed by pseudovirus neutralization assay.
  
  
  
  Priming with AdC followed by a protein boost or sequential immunizations with two AdC vectors induced HIV-1 Env-specific binding antibodies, including those to the variable region 2, whereas priming with protein followed by an AdC boost was relatively ineffective. Antibodies that cross-neutralized tier 1 HIV-1 from different subtypes were elicited with vaccine regimens that included immunizations with protein.
  
  
  
  Our study warrants further investigation of AdC vector and gp145 protein prime-boost vaccines and their ability to protect against acquisition in animal challenge studies.
authors.affiliation: aUniversity of Pennsylvania, Philadelphia bThe Wistar Institute, Philadelphia, Pennsylvania cThe Henry M. Jackson Foundation, Rockville dMilitary HIV Research Program eWalter Reed Army Institute of Research, Silver Spring, Maryland, USA.
authors.forename: Kristel L
authors.initials: KL
authors.lastname: Emmer
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wieczorek
authors.forename: Steven
authors.initials: S
authors.lastname: Tuyishime
authors.forename: Sebastian
authors.initials: S
authors.lastname: Molnar
authors.forename: Victoria R
authors.initials: VR
authors.lastname: Polonis
authors.forename: Hildegund C J
authors.initials: HC
authors.lastname: Ertl
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000915:Antibody Affinity; D000917:Antibody Formation; D004337:Drug Carriers / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood*; D007115:Immunization Schedule; D051379:Mice; D008813:Mice, Inbred ICR; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; D004337:Drug Carriers; D015483:HIV Antibodies; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C041524:aluminum sulfate