Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein.

Published

Journal Article

Our knowledge of the binding sites for neutralizing Abs (NAb) that recognize a broad range of HIV-1 strains (bNAb) has substantially increased in recent years. However, gaps remain in our understanding of how to focus B cell responses to vulnerable conserved sites within the HIV-1 envelope glycoprotein (Env). In this article, we report an immunization strategy composed of a trivalent HIV-1 (clade B envs) DNA prime, followed by a SIVmac239 gp140 Env protein boost that aimed to focus the immune response to structurally conserved parts of the HIV-1 and simian immunodeficiency virus (SIV) Envs. Heterologous NAb titers, primarily to tier 1 HIV-1 isolates, elicited during the trivalent HIV-1 env prime, were significantly increased by the SIVmac239 gp140 protein boost in rabbits. Epitope mapping of Ab-binding reactivity revealed preferential recognition of the C1, C2, V2, V3, and V5 regions. These results provide a proof of concept that a distally related retroviral SIV Env protein boost can increase pre-existing NAb responses against HIV-1.

Full Text

Duke Authors

Cited Authors

  • Uchtenhagen, H; Schiffner, T; Bowles, E; Heyndrickx, L; LaBranche, C; Applequist, SE; Jansson, M; De Silva, T; Back, JW; Achour, A; Scarlatti, G; Fomsgaard, A; Montefiori, D; Stewart-Jones, G; Spetz, A-L

Published Date

  • June 15, 2014

Published In

Volume / Issue

  • 192 / 12

Start / End Page

  • 5802 - 5812

PubMed ID

  • 24829409

Pubmed Central ID

  • 24829409

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1301898

Language

  • eng

Conference Location

  • United States