Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein.

Summary, in English

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.

• Author: 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
• Department/s: Division of Medical Microbiology
• Publishing year: 2014
• Language: English
• Pages: 5802-5812
• Publication/Series: Journal of Immunology
• Volume: 192
• Issue: 12
• Links: http://www.ncbi.nlm.nih.gov/pubmed/24829409?dopt=Abstract; http://dx.doi.org/10.4049/jimmunol.1301898
• Document type: Journal article
• Publisher: American Association of Immunologists
• Topic: Immunology in the medical area
• Status: Published
• ISBN/ISSN/Other: ISSN: 1550-6606