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 Rd, Covington, LA 70433, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Barnes
authors.affiliation: Tulane National Primate Research Center, 18703 Three Rivers Rd, 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.
authors.forename: James M
authors.initials: JM
authors.lastname: Binley
keywords: Env; HIV; VLPs; antibody; gp120; gp41; neutralization; vaccine