Journal Article

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

Zak, Daniel E, Jarvis, Michael A, Stone, Michele, Edlefsen, Paul T, Park, Haesun, Armstrong, Christina, Früh, Klaus, Messerle, Martin, Ventura, Abigail B, Ford, Julia C, Hughes, Colette M, Ainslie, Emily, Zweig, Robert C, Randall, Kurt T, Selseth, Andrea N, Alter, Galit, Picker, Louis J, Marshall, Emily E, Lu, Lenette, Xu, Guangwu, Planer, Shannon L, Turner, John M, Shankar, Smitha, Axthelm, Michael K, Bonavia, Aurelio, Lewis, Matthew S, Gilbride, Roxanne M, Sylwester, Andrew W, Evans, Thomas G, Braun, Jackie M, Laddy, Dominick J, Herlache, Lauren, Valvo, Joseph, Rundstrom, Parker, Hansen, Scott G, Malouli, Daniel, Amon, Lynn M, Fischer, Miranda, Legasse, Alfred W, Aderem, Alan

2018

Overview

Complete vaccine-mediated immune control of highly pathogenic Mycobacterium tuberculosis is possible if immune effector responses can intercept the infection at its earliest stages. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 13 / 13/31 / 38 / 38/39 / 38/91 / 631/250/590 / 631/250/590/1867 / Animals / Antigens / Bacillus Calmette-Guerin vaccine / BCG / BCG Vaccine - immunology / Biomedicine / Cancer Research / CD4 antigen / CD8 antigen / Cell culture / Comparative analysis / Computed tomography / Cytomegalovirus / Cytomegalovirus - immunology / Disease control / Disease prevention / Genetic aspects / Immunization / Immunological memory / Infections / Infectious Diseases / Inserts / Lymphocytes / Lymphocytes T / Macaca mulatta - immunology / Memory cells / Metabolic Diseases / Molecular Medicine / Monkeys & apes / Mycobacterium tuberculosis / Mycobacterium tuberculosis - immunology / Necropsy / Neurosciences / Physiological aspects / Prevention / T cells / Tuberculosis / Tuberculosis - immunology / Tuberculosis vaccines / Vaccination / Vaccines