Harnessing donor unrestricted T-cells for new vaccines against tuberculosis

for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation

Research output: Contribution to journalReview article

6 Citations (Scopus)

Abstract

Mycobacterium bovis bacille Calmette-Guérin (BCG) prevents extrapulmonary tuberculosis (TB) and death among infants but fails to consistently and sufficiently prevent pulmonary TB in adults. Thus, TB remains the leading infectious cause of death worldwide, and new vaccine approaches are urgently needed. T-cells are important for protective immunity to Mycobacterium tuberculosis (Mtb), but the optimal T-cell antigens to be included in new vaccines are not established. T-cells are often thought of as responding mainly to peptide antigens presented by polymorphic major histocompatibility complex (MHC) I and II molecules. Over the past two decades, the number of non-peptidic Mtb derived antigens for αβ and γδ T-cells has expanded rapidly, creating broader perspectives about the types of molecules that could be targeted by T-cell-based vaccines against TB. Many of these non-peptide responsive T-cell subsets in humans are activated in a manner that is unrestricted by classical MHC-dependent antigen-presenting systems, but instead require essentially nonpolymorphic presentation systems. These systems are Cluster of differentiation 1 (CD1), MHC related protein 1 (MR1), butyrophilin 3A1, as well as the nonclassical MHC class Ib family member HLA-E. Thus, the resulting T-cell responses can be shared among a genetically diverse population, creating the concept of donor-unrestricted T-cells (DURTs). Here, we review evidence that DURTs are an abundant component of the human immune system and recognize many antigens expressed by Mtb, including antigens that are expressed in BCG and other candidate whole cell vaccines. Further, DURTs exhibit functional diversity and demonstrate the ability to control microbial infection in small animal models. Finally, we outline specific knowledge gaps and research priorities that must be addressed to realize the full potential of DURTs as part of new TB vaccines approaches.

Original languageEnglish (US)
Pages (from-to)3022-3030
Number of pages9
JournalVaccine
Volume37
Issue number23
DOIs
StatePublished - May 21 2019

Fingerprint

Tuberculosis Vaccines
tuberculosis
T-lymphocytes
vaccines
T-Lymphocytes
Major Histocompatibility Complex
major histocompatibility complex
antigens
Mycobacterium tuberculosis
Vaccines
Antigens
Tuberculosis
butyrophilin
death
Aptitude
Viral Tumor Antigens
T-Lymphocyte Subsets
Cellular Structures
Infection Control
Mycobacterium bovis

Keywords

  • Donor-unrestricted T-cells
  • Tetramers
  • Tuberculosis
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation (2019). Harnessing donor unrestricted T-cells for new vaccines against tuberculosis. Vaccine, 37(23), 3022-3030. https://doi.org/10.1016/j.vaccine.2019.04.050

Harnessing donor unrestricted T-cells for new vaccines against tuberculosis. / for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation.

In: Vaccine, Vol. 37, No. 23, 21.05.2019, p. 3022-3030.

Research output: Contribution to journalReview article

for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation 2019, 'Harnessing donor unrestricted T-cells for new vaccines against tuberculosis', Vaccine, vol. 37, no. 23, pp. 3022-3030. https://doi.org/10.1016/j.vaccine.2019.04.050
for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation. Harnessing donor unrestricted T-cells for new vaccines against tuberculosis. Vaccine. 2019 May 21;37(23):3022-3030. https://doi.org/10.1016/j.vaccine.2019.04.050
for the Collaboration for Tuberculosis Vaccine Discovery - Donor-Unrestricted T-cells Working Group, Bill and Melinda Gates Foundation. / Harnessing donor unrestricted T-cells for new vaccines against tuberculosis. In: Vaccine. 2019 ; Vol. 37, No. 23. pp. 3022-3030.
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