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

Hannes Uchtenhagen, Torben Schiffner, Emma Bowles, Leo Heyndrickx, Celia La Branche, 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 journalArticle

Abstract

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 SIV mac239 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 preexisting NAb responses against HIV-1.

Original languageEnglish
Pages (from-to)5802-5812
Number of pages11
JournalJournal of Immunology
Volume192
Issue number12
DOIs
Publication statusPublished - Jun 15 2014

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Uchtenhagen, H., Schiffner, T., Bowles, E., Heyndrickx, L., La Branche, C., Applequist, S. E., Jansson, M., De Silva, T., Back, J. W., Achour, A., Scarlatti, G., Fomsgaard, A., Montefiori, D., Stewart-Jones, G., & Spetz, A. L. (2014). Boosting of HIV-1 neutralizing antibody responses by a distally related retroviral envelope protein. Journal of Immunology, 192(12), 5802-5812. https://doi.org/10.4049/jimmunol.1301898