2. Academic Validation
  3. Efficacy of ABX196, a new NKT agonist, in prophylactic human vaccination

Efficacy of ABX196, a new NKT agonist, in prophylactic human vaccination

  • Vaccine. 2014 Oct 21;32(46):6138-45. doi: 10.1016/j.vaccine.2014.08.070.
Josianne Nitcheu Tefit 1,  Sandrine Crabé 2,  Bernard Orlandini 3,  Haylene Nell 4,  Albert Bendelac 5,  Shenglou Deng 6,  Paul B Savage 7,  Luc Teyton 8,  Vincent Serra 9
Affiliations

Affiliations

  • 1 Abivax, 5 rue Henri Desbruères, 91030 Evry cedex, France. Electronic address: Josianne.nitcheu@abivax.com.
  • 2 Abivax, 5 rue Henri Desbruères, 91030 Evry cedex, France. Electronic address: sandrine.crabe@abivax.com.
  • 3 Phinc, 5, rue Henri Desbruères Immeuble Genavenir 8 91030 Evry, France. Electronic address: bernard.orlandini@phinc.fr.
  • 4 Tiervlei Trial Centre, Karl Bremer Hospital, Bellville, 7530 South Africa. Electronic address: haylenenell@ttctrials.co.za.
  • 5 Committee on Immunology and Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA. Electronic address: abendela@bsd.uchicago.edu.
  • 6 Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA. Electronic address: sdeng@chem.byu.edu.
  • 7 Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA. Electronic address: paul_savage@byu.edu.
  • 8 Department of Immunology and Microbial science, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: lteyton@scripps.edu.
  • 9 Abivax, 5 rue Henri Desbruères, 91030 Evry cedex, France. Electronic address: vincent.serra@abivax.com.
PMID: 25218293 DOI: 10.1016/j.vaccine.2014.08.070
Abstract

We have assessed the immune-regulatory and Adjuvant activities of a synthetic glycolipid, ABX196, a novel analog of the parental compound α-GalCer. As expected, ABX196 demonstrated a measurable and significant Adjuvant effect in mice and monkeys with no appreciable toxicity at the doses used to promote immune responses. We performed a phase I/II dose escalation study of ABX196 in healthy volunteers, with the objectives to evaluate its safety profile, as well as its ability to be utilized as an Adjuvant in the context of a prophylactic vaccine against hepatitis B. ABX196 was administered at three doses: 0.2, 0.4, and 2.0μg, in 44 subjects. In all the individuals injected with ABX196, peripheral blood NKT cells displayed hallmarks of activation, and 45% of them had measurable circulating IFN-γ 24h after the first administration. More importantly, the addition of ABX196 to the very poorly immunogenic HBs antigen resulted in protective anti-HBs antibody responses in majority of patients, demonstrating the Adjuvant properties of ABX196 in human. Further analysis of the cohort of subjects receiving ABX196 with HBs antigen also indicates that a single injection appears sufficient to provide protection. A limited set of adverse events linked to the systemic delivery of ABX196 and access to the liver, is discussed in the context of formulation and the need to limit transport of ABX196 to secondary lymphoid tissues for maximal efficacy (Eudra-CT 2012-001566-15).

Keywords

ABX196; Adjuvant; Glycolipid; NKT cells; α-GalCer.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-156997
    NKT 激动剂
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