title: Cross-clade HIV-1 neutralizing antibodies induced with V3-scaffold protein immunogens following priming with gp120 DNA.
abstract: The V3 epitope is a known target for HIV-1 neutralizing antibodies (NAbs), and V3-scaffold fusion proteins used as boosting immunogens after gp120 DNA priming were previously shown to induce NAbs in rabbits. Here, we evaluated whether the breadth and potency of the NAb response could be improved when boosted with rationally designed V3-scaffold immunogens. Rabbits were primed with codon-optimized clade C gp120 DNA and boosted with one of five V3-cholera toxin B fusion proteins (V3-CTBs) or with double combinations of these. The inserts in these immunogens were designed to display V3 epitopes shared by the majority of global HIV-1 isolates. Double combinations of V3-CTB immunogens generally induced more broad and potent NAbs than did boosts with single V3-CTB immunogens, with the most potent and broad NAbs elicited with the V3-CTB carrying the consensus V3 of clade C (V3(C)-CTB), or with double combinations of V3-CTB immunogens that included V3(C)-CTB. Neutralization of tier 1 and 2 pseudoviruses from clades AG, B, and C and of peripheral blood mononuclear cell (PBMC)-grown primary viruses from clades A, AG, and B was achieved, demonstrating that priming with gp120 DNA followed by boosts with V3-scaffold immunogens effectively elicits cross-clade NAbs. Focusing on the V3 region is a first step in designing a vaccine targeting protective epitopes, a strategy with potential advantages over the use of Env, a molecule that evolved to protect the virus by poorly inducing NAbs and by shielding the epitopes that are most critical for infectivity.
authors.affiliation: Veterans Affairs Medical Center, New York, NY, USA. zollas01@med.nyu.edu
authors.forename: Susan
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: X-P
authors.initials: XP
authors.lastname: Kong
authors.forename: Xunqing
authors.initials: X
authors.lastname: Jiang
authors.forename: Timothy
authors.initials: T
authors.lastname: Cardozo
authors.forename: Arthur
authors.initials: A
authors.lastname: Nádas
authors.forename: Sandra
authors.initials: S
authors.lastname: Cohen
authors.forename: Maxim
authors.initials: M
authors.lastname: Totrov
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods*; D011817:Rabbits; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; C514793:gp120 protein, Human immunodeficiency virus 1