title: Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques.
abstract: Virus-like particles (VLPs) offer a platform to test the hypothesis that, since antibody binding to native envelope glycoprotein (Env) trimers results in HIV-1 neutralization, that native Env trimers presented in membranes may be useful for inducing neutralizing antibodies (nAbs) in a vaccine setting. So far, VLPs have not fulfilled this potential. Here, using a "shotgun" approach, we evaluated a wide cross-section of variables in a series of VLP immunizations. We identified 3 tentative leads. First, that VLP doses may not have been sufficient for optimal nAb induction. Second, that dampening the antigenicity of non-functional Env (for example uncleaved gp160) using either protease digests or IgG masking may be useful. Third, that guinea pig sera preferentially target non-conserved epitopes and exhibit relatively high background activity, suggesting that rabbits may be preferable as small animal vaccine models. Recent immunogenicity studies in rabbits appear to bear out all 3 of these leads.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
authors.forename: Tommy
authors.initials: T
authors.lastname: Tong
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
authors.forename: Ema T
authors.initials: ET
authors.lastname: Crooks
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Osawa
authors.affiliation: Tulane University, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Barnes
authors.affiliation: Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA.
authors.forename: Cristian
authors.initials: C
authors.lastname: Apetrei
authors.affiliation: Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA. Electronic address: jbinley@tpims.org.
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D005260:Female; D006168:Guinea Pigs; D015483:HIV Antibodies / Q000097:blood*; D015497:HIV-1 / Q000276:immunology*; D008253:Macaca mulatta; D008297:Male; D023421:Models, Animal; D011817:Rabbits; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D058425:Vaccines, Virus-Like Particle
keywords: Antibody; Env; HIV; Neutralization; VLPs; Vaccine; gp120; gp41