Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells

Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope

Catherine Fayolle, Maryline Davi, Hui Dong, Dorothea Ritzel, Aurélie Le Page, Friederike Knipping, Laleh Majlessi, Daniel Ladant, Claude Leclerc

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

HIV-Tat based vaccines have been proposed as an attractive option to prevent or treat AIDS. A vaccine to induce optimal anti-Tat neutralizing antibody responses was designed by inserting this protein, or its dominant B-cell epitope, into the CyaA vector, which targets dendritic cells (DC). Tat was inserted into various sites of CyaA, including regions that do not translocate into the cytosol of the targeted DC. The presentation of the Tat CD4+ T-cell epitope delivered by the CyaA-Tat proteins was observed with a recombinant CyaA in which the entire AC domain was replaced by the entire Tat protein (Tat-Δ373 CyaA) but was abolished with large deletions of the N-terminal region. Moreover, CyaA carrying multiple copies of the dominant Tat: 1-21 B-cell epitope were shown to induce high titers of anti-Tat antibodies, even after a single immunization, that persisted up to 10 weeks post-immunization.

Original languageEnglish (US)
Pages (from-to)6930-6941
Number of pages12
JournalVaccine
Volume28
Issue number42
DOIs
StatePublished - Oct 1 2010

Fingerprint

tat Gene Products
B-Lymphocyte Epitopes
dendritic cells
Neutralizing Antibodies
neutralizing antibodies
Dendritic Cells
epitopes
B-lymphocytes
Immunization
Vaccines
T-Lymphocyte Epitopes
immunization
Cytosol
vaccines
Antibody Formation
Anti-Idiotypic Antibodies
Acquired Immunodeficiency Syndrome
proteins
HIV
cytosol

Keywords

  • Adenylate cyclase
  • B-cell epitope
  • HIV-Tat
  • Neutralizing antibodies

Cite this

Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells : Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope. / Fayolle, Catherine; Davi, Maryline; Dong, Hui; Ritzel, Dorothea; Le Page, Aurélie; Knipping, Friederike; Majlessi, Laleh; Ladant, Daniel; Leclerc, Claude.

In: Vaccine, Vol. 28, No. 42, 01.10.2010, p. 6930-6941.

Research output: Contribution to journalArticle

Fayolle, Catherine ; Davi, Maryline ; Dong, Hui ; Ritzel, Dorothea ; Le Page, Aurélie ; Knipping, Friederike ; Majlessi, Laleh ; Ladant, Daniel ; Leclerc, Claude. / Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells : Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope. In: Vaccine. 2010 ; Vol. 28, No. 42. pp. 6930-6941.
@article{7cd971231d754742b17169beaa91205c,
title = "Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells: Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope",
abstract = "HIV-Tat based vaccines have been proposed as an attractive option to prevent or treat AIDS. A vaccine to induce optimal anti-Tat neutralizing antibody responses was designed by inserting this protein, or its dominant B-cell epitope, into the CyaA vector, which targets dendritic cells (DC). Tat was inserted into various sites of CyaA, including regions that do not translocate into the cytosol of the targeted DC. The presentation of the Tat CD4+ T-cell epitope delivered by the CyaA-Tat proteins was observed with a recombinant CyaA in which the entire AC domain was replaced by the entire Tat protein (Tat-Δ373 CyaA) but was abolished with large deletions of the N-terminal region. Moreover, CyaA carrying multiple copies of the dominant Tat: 1-21 B-cell epitope were shown to induce high titers of anti-Tat antibodies, even after a single immunization, that persisted up to 10 weeks post-immunization.",
keywords = "Adenylate cyclase, B-cell epitope, HIV-Tat, Neutralizing antibodies",
author = "Catherine Fayolle and Maryline Davi and Hui Dong and Dorothea Ritzel and {Le Page}, Aur{\'e}lie and Friederike Knipping and Laleh Majlessi and Daniel Ladant and Claude Leclerc",
year = "2010",
month = "10",
day = "1",
doi = "10.1016/j.vaccine.2010.07.059",
language = "English (US)",
volume = "28",
pages = "6930--6941",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "42",

}

TY - JOUR

T1 - Induction of anti-Tat neutralizing antibodies by the CyaA vector targeting dendritic cells

T2 - Influence of the insertion site and of the delivery of multicopies of the dominant Tat B-cell epitope

AU - Fayolle, Catherine

AU - Davi, Maryline

AU - Dong, Hui

AU - Ritzel, Dorothea

AU - Le Page, Aurélie

AU - Knipping, Friederike

AU - Majlessi, Laleh

AU - Ladant, Daniel

AU - Leclerc, Claude

PY - 2010/10/1

Y1 - 2010/10/1

N2 - HIV-Tat based vaccines have been proposed as an attractive option to prevent or treat AIDS. A vaccine to induce optimal anti-Tat neutralizing antibody responses was designed by inserting this protein, or its dominant B-cell epitope, into the CyaA vector, which targets dendritic cells (DC). Tat was inserted into various sites of CyaA, including regions that do not translocate into the cytosol of the targeted DC. The presentation of the Tat CD4+ T-cell epitope delivered by the CyaA-Tat proteins was observed with a recombinant CyaA in which the entire AC domain was replaced by the entire Tat protein (Tat-Δ373 CyaA) but was abolished with large deletions of the N-terminal region. Moreover, CyaA carrying multiple copies of the dominant Tat: 1-21 B-cell epitope were shown to induce high titers of anti-Tat antibodies, even after a single immunization, that persisted up to 10 weeks post-immunization.

AB - HIV-Tat based vaccines have been proposed as an attractive option to prevent or treat AIDS. A vaccine to induce optimal anti-Tat neutralizing antibody responses was designed by inserting this protein, or its dominant B-cell epitope, into the CyaA vector, which targets dendritic cells (DC). Tat was inserted into various sites of CyaA, including regions that do not translocate into the cytosol of the targeted DC. The presentation of the Tat CD4+ T-cell epitope delivered by the CyaA-Tat proteins was observed with a recombinant CyaA in which the entire AC domain was replaced by the entire Tat protein (Tat-Δ373 CyaA) but was abolished with large deletions of the N-terminal region. Moreover, CyaA carrying multiple copies of the dominant Tat: 1-21 B-cell epitope were shown to induce high titers of anti-Tat antibodies, even after a single immunization, that persisted up to 10 weeks post-immunization.

KW - Adenylate cyclase

KW - B-cell epitope

KW - HIV-Tat

KW - Neutralizing antibodies

UR - http://www.scopus.com/inward/record.url?scp=77956870448&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956870448&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2010.07.059

DO - 10.1016/j.vaccine.2010.07.059

M3 - Article

VL - 28

SP - 6930

EP - 6941

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 42

ER -