@article{ea9ac6cc617c451b93ed5845649e11f1,
title = "Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine",
abstract = "Despite widespread use of the bacille Calmette-Gu{\'e}rin (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.",
author = "Hansen, {Scott G.} and Zak, {Daniel E.} and Guangwu Xu and Ford, {Julia C.} and Marshall, {Emily E.} and Daniel Malouli and Gilbride, {Roxanne M.} and Hughes, {Colette M.} and Ventura, {Abigail B.} and Emily Ainslie and Randall, {Kurt T.} and Selseth, {Andrea N.} and Parker Rundstrom and Lauren Herlache and Lewis, {Matthew S.} and Haesun Park and Planer, {Shannon L.} and Turner, {John M.} and Miranda Fischer and Christina Armstrong and Zweig, {Robert C.} and Joseph Valvo and Braun, {Jackie M.} and Smitha Shankar and Lenette Lu and Sylwester, {Andrew W.} and Legasse, {Alfred W.} and Martin Messerle and Jarvis, {Michael A.} and Amon, {Lynn M.} and Alan Aderem and Galit Alter and Laddy, {Dominick J.} and Michele Stone and Aurelio Bonavia and Evans, {Thomas G.} and Axthelm, {Michael K.} and Klaus Fr{\"u}h and Edlefsen, {Paul T.} and Picker, {Louis J.}",
note = "Funding Information: We thank C. Kahl, S. Hagen, J. Bae, I. Pelletier, Y. Guo, E.M. Borst, L.S. Uebelhoer and J. Womack for technical assistance, C. Scanga and J. Flynn for guidance on the RM model of TB (including sharing of NHP protocols and provision of Mtb challenge stocks), P. Barry (University of California, Davis) and T. Shenk (Princeton University) for the 68-1 and 68-1.2 BACs, respectively, J. Flynn (University of Pittsburgh) for Mtb Erdman, W. Hanekom, L. Stuart and D. Barber for helpful discussions, D. Casimiro for manuscript review, J. Strussenberg for management of the BSL3 facility, L. Boshears for administrative assistance and A. Townsend for figure preparation. This work was supported by AERAS, the Bill and Melinda Gates Foundation (grant no. OPP1087783; A.A. and D.E.Z.) and the US National Institutes of Health (NIH; grant no. U19 AI106761 (A.A.), P51 OD011092 (ONPRC); U42 OD010426 (ONPRC)).",
year = "2018",
month = feb,
day = "1",
doi = "10.1038/nm.4473",
language = "English (US)",
volume = "24",
pages = "130--143",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "2",
}