First in humans: a new molecularly defined vaccine shows excellent safety and strong induction of long-lived Mycobacterium tuberculosis-specific Th1-cell like responses

Hum Vaccin. 2010 Dec;6(12):1007-15. doi: 10.4161/hv.6.12.13143. Epub 2010 Dec 1.

Abstract

Tuberculosis (TB) remains a major killer worldwide. The only available TB-vaccine, the nearly century-old Mycobacterium bovis BCG, has had only a limited effect on TB incidence. Therefore, developing new TB vaccines is a key priority, and the first new generation TB vaccines are now being tested in clinical trials. Here we describe the development and first testing in humans of a novel, wholly synthetic TB subunit vaccine. This vaccine has proven safe and highly immunogenic in all species in which it was tested, including mice, guinea pigs, non-human primates and humans. Most encouragingly, following vaccination in humans, strong IFN-γ responses persisted through at least 2½ years of follow-up, indicating induction of a substantial memory response by this new TB vaccine. These findings encourage further preclinical and clinical studies with TB subunit vaccines and cellular immunity-stimulating new adjuvants.

Trial registration: ClinicalTrials.gov NCT01003093.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Guinea Pigs
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mycobacterium tuberculosis / immunology*
  • Th1 Cells / immunology*
  • Time Factors
  • Tuberculosis Vaccines / adverse effects*
  • Tuberculosis Vaccines / chemistry
  • Tuberculosis Vaccines / immunology*
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / chemistry
  • Vaccines, Synthetic / immunology

Substances

  • Tuberculosis Vaccines
  • Vaccines, Subunit
  • Vaccines, Synthetic
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT01003093