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

doi:10.1016/j.vaccine.2010.07.059

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

Stem Cell Institute

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Pages (from-to)	6930-6941
Number of pages	12
Journal	Vaccine
Volume	28
Issue number	42
DOIs	https://doi.org/10.1016/j.vaccine.2010.07.059
State	Published - Oct 2010

Bibliographical note

Funding Information:
The CyaAE5-Alexa Fluor 488 was a kind gift of Dr. Peter Sebo (Institute of Microbiology of the Academy of Sciences, Prague, Czech Republic). We thank Emmanuel Frachon from the Plate-Forme 5 “Production de Protéines Recombinantes et d’Anticorps” at the Pasteur Institute for expert assistance in bacterial cell growth in fermentors. This work was supported by the French National Agency for Research on AIDS and by the Ligue Nationale Contre le Cancer (Equipe Labellisée 2007) .

Keywords

Adenylate cyclase
B-cell epitope
HIV-Tat
Neutralizing antibodies

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vaccine.2010.07.059

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Fayolle, C., Davi, M., Dong, H., Ritzel, D., Le Page, A., Knipping, F., Majlessi, L., Ladant, D., & Leclerc, C. (2010). 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. Vaccine, 28(42), 6930-6941. https://doi.org/10.1016/j.vaccine.2010.07.059

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 et al.
In: Vaccine, Vol. 28, No. 42, 10.2010, p. 6930-6941.

Research output: Contribution to journal › Article › peer-review

Fayolle, C, Davi, M, Dong, H, Ritzel, D, Le Page, A, Knipping, F, Majlessi, L, Ladant, D & Leclerc, C 2010, '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', Vaccine, vol. 28, no. 42, pp. 6930-6941. https://doi.org/10.1016/j.vaccine.2010.07.059

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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.",

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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",

note = "Funding Information: The CyaAE5-Alexa Fluor 488 was a kind gift of Dr. Peter Sebo (Institute of Microbiology of the Academy of Sciences, Prague, Czech Republic). We thank Emmanuel Frachon from the Plate-Forme 5 “Production de Prot{\'e}ines Recombinantes et d{\textquoteright}Anticorps” at the Pasteur Institute for expert assistance in bacterial cell growth in fermentors. This work was supported by the French National Agency for Research on AIDS and by the Ligue Nationale Contre le Cancer (Equipe Labellis{\'e}e 2007) . ",

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AU - Ladant, Daniel

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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

Bibliographical note

Keywords

UN SDGs

Publisher link

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