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
C2 - 20728521
AN - SCOPUS:77956870448
VL - 28
SP - 6930
EP - 6941
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 42
ER -