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

Vaccine. 2014 Dec 12;32(52):7098-107. doi: 10.1016/j.vaccine.2014.10.036. Epub 2014 Oct 30.

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.

Keywords: Adjuvant; Clinical trial; Immunogenicity; Tuberculosis; Vaccine.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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