Journal
NATURE MEDICINE
Volume 24, Issue 2, Pages 130-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nm.4473
Keywords
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Funding
- AERAS
- Bill and Melinda Gates Foundation [OPP1087783]
- US National Institutes of Health (NIH)
- US National Institutes of Health (ONPRC) [U19 AI106761, P51 OD011092, U42 OD010426]
- Bill and Melinda Gates Foundation [OPP1087783] Funding Source: Bill and Melinda Gates Foundation
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Despite widespread use of the bacille Calmette-Guerin (BCG) vaccine, tuberculosis (TB) remains a leading cause of global mortality from a single infectious agent (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs) with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter referred to as RhCMV/TB)-which elicit and maintain highly effector-differentiated, circulating and tissue-resident Mtb-specific CD4(+) and CD8(+) memory T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of Mtb infection and disease by 68%, as compared to that in unvaccinated controls, after intrabronchial challenge with the Erdman strain of Mtb at similar to 1 year after the first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both studies showed no TB disease by computed tomography scans or at necropsy after challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs were Mtb-culture-negative for all tissues, an exceptional long-term vaccine effect in the RM challenge model with the Erdman strain of Mtb. These results suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is possible if immune effector responses can intercept Mtb infection at its earliest stages.
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