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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Delivery of the HIV-1 Tat protein to dendritic cells by the CyaA vector induces specific Th1 responses and high affinity neutralizing antibodies in non human primates
Vaccine, Volume 24, No. 17, Year 2006
Notification
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Description
The human immunodeficiency virus type 1 (HIV-1) Tat is a key protein playing a major role in the infectivity of the virus. Thus, HIV-Tat based vaccines have been proposed as an attractive option to treat AIDS. Recently, we have shown that the recombinant detoxified adenylate cyclase (CyaA) from Bordetella pertussis carrying HIV-Tat (CyaA-E5-Tat), targets dendritic cells (DCs) and induces specific Th1 polarized and neutralizing antibody responses in mice. To further explore the potentialities of this prototype vaccine for human use, we analyzed the CyaA-E5-Tat induced antibody responses in non-human primates and established the biological characteristics of these antibodies. African Green Monkeys (AGM) were immunized with CyaA-E5-Tat in the presence or in the absence of alum adjuvant. First, we showed that the anti-CyaA antibodies induced by such immunization does not interfere with the binding of CyaA-E5-Tat to its receptor at the DC surface, the αMβ2 integrin. Monkeys immunized with CyaA-E5-Tat, with or without alum, produced anti-Tat antibodies that mainly recognized the N-terminal domain of the Tat protein. Importantly, all sera obtained after three immunizations displayed the capacity to bind to Tat and neutralize its transactivating function in vitro. Finally, in the absence of alum, CyaA-E5-Tat, induced Th1 Tat specific T cell responses. These findings reveal that CyaA-E5-Tat is efficiently delivered in non-human primates and had a significant impact on the generation of neutralizing anti-Tat antibodies. These observations are, thus, encouraging for the use of the CyaA vector in human and also suggest that CyaA-E5-Tat might be a useful tool to decipher the biological characteristic of such antibodies. © 2006 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Mascarell, Laurent
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
Bauche, Cecile
France, Paris
Institut Pasteur, Paris
Fayolle, Catherine
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
Diop, Ousmane Madiagne
Senegal, Dakar
Institut Pasteur de Dakar
Dupuy, Monique
France, Lyon
Sanofi Pasteur sa
Nougarede, Nolwenn
France, Lyon
Sanofi Pasteur sa
Perraut, Ronald
Senegal, Dakar
Institut Pasteur de Dakar
Ladant, Daniel
France, Paris
Institut Pasteur, Paris
Leclerc, Claude D.
France, Paris
Institut Pasteur, Paris
France, Paris
Inserm
Statistics
Citations: 24
Authors: 9
Affiliations: 4
Identifiers
Doi:
10.1016/j.vaccine.2006.02.009
ISSN:
0264410X
Research Areas
Infectious Diseases
Maternal And Child Health