Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primatesResearch in context
Elise Ishida,
Devin T. Corrigan,
Tingting Chen,
Yanyan Liu,
Ryung S. Kim,
Lusheng Song,
Tara M. Rutledge,
D Mitchell Magee,
Joshua LaBaer,
Todd L. Lowary,
Philana Ling Lin,
Jacqueline M. Achkar
Affiliations
Elise Ishida
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Devin T. Corrigan
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
Tingting Chen
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
Yanyan Liu
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Ryung S. Kim
Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY, USA
Lusheng Song
Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
Tara M. Rutledge
Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
D Mitchell Magee
Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
Joshua LaBaer
Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, Tempe, AZ, USA
Todd L. Lowary
Department of Chemistry, University of Alberta, Edmonton, AB, Canada; Institute of Biological Chemistry, Academia Sinica, Nangang Taipei, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan
Philana Ling Lin
Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Jacqueline M. Achkar
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA; Corresponding author. Departments of Medicine, and Microbiology & Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Block Bld., Rm. 115, Bronx, NY, 10461, USA.
Summary: Background: Increasing evidence supports that antibodies can protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially in the airways, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) versus uncontrolled infection (TB) in nonhuman primates. Methods: In a case–control design, using non-parametric group comparisons with false discovery rate adjustments, we assessed antibodies in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to, two-, and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays. Findings: Macaques that developed LTBI (n = 36) had significantly increased airway and plasma IgA reactivities to specific arabinomannan (AM) motifs prior to Mtb infection compared to those that developed TB (n = 21; p < 0.01, q < 0.05). Furthermore, LTBI macaques had higher plasma IgG reactivity to protein MTB32A (Rv0125) early post Mtb infection (p < 0.05) and increasing airway IgG responses to some proteins over time. Interpretation: Our results support a protective role of pre-existing mucosal (lung) and systemic IgA to specific Mtb glycan motifs, suggesting that prior exposure to nontuberculous mycobacteria could be protective against TB. They further suggest that IgG to Mtb proteins early post infection could provide an additional protective mechanism. These findings could inform TB vaccine development strategies. Funding: NIH/NIAID AI117927, AI146329, and AI127173 to JMA.
