A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human.

Abstract

Here, we report on a first-in-man trial where the tuberculosis (TB) vaccine Ag85B-ESAT-6 (H1) was adjuvanted with escalating doses of a novel liposome adjuvant CAF01. On their own, protein antigens cannot sufficiently induce immune responses in humans, and require the addition of an adjuvant system to ensure appropriate delivery and concomitant immune activation. To date no approved adjuvants are available for induction of cellular immunity, which seems essential for a number of vaccines, including vaccines against TB. We vaccinated four groups of human volunteers: a non-adjuvanted H1 group, followed by three groups with escalating doses of CAF01-adjuvanted H1 vaccine. All subjects were vaccinated at 0 and 8 weeks and followed up for 150 weeks. Vaccination did not cause local or systemic adverse effects besides transient soreness at the injection site. Two vaccinations elicited strong antigen-specific T-cell responses which persisted after 150 weeks follow-up, indicating the induction of a long-lasting memory response in the vaccine recipients. These results show that CAF01 is a safe and tolerable, Th1-inducing adjuvant for human TB vaccination trials and for vaccination studies in general where cellular immunity is required.

• Authors: Jaap T van Dissel, Simone A Joosten, Søren T Hoff, Darius Soonawala, Corine Prins, David A Hokey, Dawn M O'Dee, Andrew Graves, Birgit Thierry-Carstensen, Lars V Andreasen, Morten Ruhwald, Adriëtte W de Visser, Else Marie Agger, Tom H M Ottenhoff, Ingrid Kromann, Peter Andersen
• Journal: Vaccine (Vaccine) Vol. 32 Issue 52 Pg. 7098-107 (Dec 12 2014) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 25454872 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Ag85B-ESAT-6 fusion antigen
• Liposomes
• Recombinant Fusion Proteins
• Tuberculosis Vaccines

Topics

• Adjuvants, Immunologic (administration & dosage, adverse effects)
• Adolescent
• Adult
• Female
• Healthy Volunteers
• Humans
• Immunologic Memory
• Liposomes (administration & dosage)
• Male
• Middle Aged
• Mycobacterium tuberculosis (immunology)
• Recombinant Fusion Proteins (administration & dosage, immunology, toxicity)
• T-Lymphocytes (immunology)
• Tuberculosis Vaccines (administration & dosage, adverse effects, immunology)
• Young Adult