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

Hannes Uchtenhagen, Torben Schiffner, Emma Bowles, Leo Heyndrickx, Celia LaBranche, Steven E Applequist, Marianne Jansson, Thushan De Silva, Jaap Willem Back, Adnane Achour, Gabriella Scarlatti, Anders Fomsgaard, David Montefiori, Guillaume Stewart-Jones, Anna-Lena Spetz

Research output: Contribution to journalA1: Web of Science-articlepeer-review


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.

Original languageEnglish
JournalJournal of Immunology
Issue number12
Pages (from-to)5802-5812
Number of pages11
Publication statusPublished - 2014


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