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

被引：190

作者：

Hansen, Scott G. ^{[1
,2
]}

Zak, Daniel E. ^{[3
]}

Xu, Guangwu ^{[1
,2
]}

Ford, Julia C. ^{[1
,2
]}

Marshall, Emily E. ^{[1
,2
]}

Malouli, Daniel ^{[1
,2
]}

Gilbride, Roxanne M. ^{[1
,2
]}

Hughes, Colette M. ^{[1
,2
]}

Ventura, Abigail B. ^{[1
,2
]}

Ainslie, Emily ^{[1
,2
]}

Randall, Kurt T. ^{[1
,2
]}

Selseth, Andrea N. ^{[1
,2
]}

Rundstrom, Parker ^{[1
,2
]}

Herlache, Lauren ^{[1
,2
]}

Lewis, Matthew S. ^{[1
,2
]}

Park, Haesun ^{[1
,2
]}

Planer, Shannon L. ^{[1
,2
]}

Turner, John M. ^{[1
,2
]}

Fischer, Miranda ^{[1
,2
]}

Armstrong, Christina ^{[1
,2
]}

Zweig, Robert C. ^{[1
,2
]}

Valvo, Joseph ^{[3
]}

Braun, Jackie M. ^{[3
]}

Shankar, Smitha ^{[3
]}

Lu, Lenette ^{[4
,5
]}

Sylwester, Andrew W. ^{[1
,2
]}

Legasse, Alfred W. ^{[1
,2
]}

Messerle, Martin ^{[6
]}

Jarvis, Michael A. ^{[7
]}

Amon, Lynn M. ^{[3
]}

Aderem, Alan ^{[3
]}

Alter, Galit ^{[4
,5
]}

Laddy, Dominick J. ^{[8
]}

Stone, Michele ^{[8
]}

Bonavia, Aurelio ^{[8
]}

Evans, Thomas G. ^{[8
]}

Axthelm, Michael K. ^{[1
,2
]}

Fruh, Klaus ^{[1
,2
]}

Edlefsen, Paul T. ^{[9
]}

Picker, Louis J. ^{[1
,2
]}

机构：

[1] OHSU, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA

[2] OHSU, ONPRC, Beaverton, OR 97006 USA

[3] Ctr Infect Dis Res, Seattle, WA USA

[4] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] Harvard Univ, Cambridge, MA 02138 USA

[6] Hannover Med Sch, Dept Virol, Hannover, Germany

[7] Univ Plymouth, Sch Biomed & Healthcare Sci, Plymouth, Devon, England

[8] Aeras, Rockville, MD USA

[9] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA

来源：

NATURE MEDICINE | 2018年 / 24卷 / 02期

基金：

美国国家卫生研究院;

关键词：

BACILLUS-CALMETTE-GUERIN; HIGHLY PATHOGENIC SIV; T-CELL RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; AEROSOL VACCINATION; BACTERIAL LOAD; INFECTION; CYNOMOLGUS; PROTECTION; NEUTROPHILS;

D O I：

10.1038/nm.4473

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：130 / +

页数：21

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