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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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Contribution to journal
publication status
published
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in
Journal of Immunology
volume
192
issue
12
pages
5802 - 5812
publisher
American Association of Immunologists
external identifiers
  • pmid:24829409
  • wos:000337172100040
  • scopus:84902181476
ISSN
1550-6606
DOI
10.4049/jimmunol.1301898
language
English
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yes
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92238bc3-6e13-46fc-bf77-2ffff29e72b1 (old id 4455138)
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http://www.ncbi.nlm.nih.gov/pubmed/24829409?dopt=Abstract
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2014-06-04 20:42:10
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2017-02-26 03:11:55
@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},
  volume       = {192},
  year         = {2014},
}