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

Uchtenhagen, Hannes ; Schiffner, Torben ; Bowles, Emma ; Heyndrickx, Leo ; LaBranche, Celia ; Applequist, Steven E ; Jansson, Marianne LU ; De Silva, Thushan ; Back, Jaap Willem and Achour, Adnane , et al. (2014) In Journal of Immunology 192(12). p.5802-5812
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
192
issue
12
pages
5802 - 5812
publisher
American Association of Immunologists
external identifiers
  • pmid:24829409
  • wos:000337172100040
  • scopus:84902181476
  • pmid:24829409
ISSN
1550-6606
DOI
10.4049/jimmunol.1301898
language
English
LU publication?
yes
id
92238bc3-6e13-46fc-bf77-2ffff29e72b1 (old id 4455138)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24829409?dopt=Abstract
date added to LUP
2016-04-01 10:30:44
date last changed
2022-02-02 18:30:22
@article{92238bc3-6e13-46fc-bf77-2ffff29e72b1,
  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 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       = {{Uchtenhagen, Hannes and Schiffner, Torben and Bowles, Emma and Heyndrickx, Leo and LaBranche, Celia and Applequist, Steven E and Jansson, Marianne and De Silva, Thushan and Back, Jaap Willem and Achour, Adnane and Scarlatti, Gabriella and Fomsgaard, Anders and Montefiori, David and Stewart-Jones, Guillaume and Spetz, Anna-Lena}},
  issn         = {{1550-6606}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{5802--5812}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{Boosting of HIV-1 Neutralizing Antibody Responses by a Distally Related Retroviral Envelope Protein.}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.1301898}},
  doi          = {{10.4049/jimmunol.1301898}},
  volume       = {{192}},
  year         = {{2014}},
}