Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine.

TitlePrevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine.
Publication TypeJournal Article
Year of Publication2018
AuthorsHansen SG, Zak DE, Xu G, Ford JC, Marshall EE, Malouli D, Gilbride RM, Hughes CM, Ventura AB, Ainslie E, Randall KT, Selseth AN, Rundstrom P, Herlache L, Lewis MS, Park H, Planer SL, Turner JM, Fischer M, Armstrong C, Zweig RC, Valvo J, Braun JM, Shankar S, Lu L, Sylwester AW, Legasse AW, Messerle M, Jarvis MA, Amon LM, Aderem A, Alter G, Laddy DJ, Stone M, Bonavia A, Evans TG, Axthelm MK, Früh K, Edlefsen PT, Picker LJ
JournalNat Med
Volume24
Issue2
Pagination130-143
Date Published2018 Feb
ISSN1546-170X
Abstract

Despite widespread use of the bacille Calmette-Guérin (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 ∼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.

DOI10.1038/nm.4473
Alternate JournalNat. Med.
PubMed ID29334373
PubMed Central IDPMC5909823
Grant ListP51 OD011092 / OD / NIH HHS / United States
U19 AI106761 / AI / NIAID NIH HHS / United States
U42 OD010426 / OD / NIH HHS / United States