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.
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.
Fayolle
Catherine
C
Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, Paris, France.
Davi
Maryline
M
Dong
Hui
H
Ritzel
Dorothea
D
Le Page
Aurélie
A
Knipping
Friederike
F
Majlessi
Laleh
L
Ladant
Daniel
D
Leclerc
Claude
C
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D037361:Adenylate Cyclase Toxin / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D017951:Antigen Presentation; D016466:CHO Cells; D018899:CpG Islands; D006224:Cricetinae; D003412:Cricetulus; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011070:Poly I-C / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D037361:Adenylate Cyclase Toxin; D057134:Antibodies, Neutralizing; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D011994:Recombinant Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D011070:Poly I-C