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
Laurent MascarellClaude Leclerc

Abstract

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 alphaMbeta2 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 it...Continue Reading

Citations

Sep 6, 2014·Nature Reviews. Immunology·Wolfgang KastenmüllerRobert A Seder
Oct 26, 2006·Nature Reviews. Immunology·Li Wu, Vineet N KewalRamani
Apr 17, 2007·Médecine sciences : M/S·Claude Leclerc
Oct 9, 2009·International Reviews of Immunology·Antonella CaputoBarbara Ensoli
Jun 5, 2007·Expert Review of Vaccines·Clint S SchmidtNadeem A Sheikh
Aug 5, 2014·Expert Review of Vaccines·Peter SeboJiri Masin
Mar 16, 2007·Expert Opinion on Emerging Drugs·Emma J Bishop, Benjamin P Howden
Nov 27, 2015·Pathogens and Disease·Masaaki Iwaki, Toshifumi Konda
Dec 13, 2007·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Nov 23, 2017·Medical Microbiology and Immunology·Dorji DorjiTrilochan K Mukkur
Mar 16, 2007·Expert Opinion on Emerging Drugs·Fausto TittiBarbara Ensoli

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