RT Journal Article SR Electronic T1 Antibody-based vaccine for tuberculosis: validation in horse foals challenged with the TB-related pathogen Rhodococcus equi JF bioRxiv FD Cold Spring Harbor Laboratory SP 292946 DO 10.1101/292946 A1 C. Cywes-Bentley A1 J. N. Rocha A1 A. I. Bordin A1 M. Vinacur A1 S. Rehman A1 T.S. Zaidi A1 M. Meyer A1 S. Anthony A1 M. Lambert A1 D. R. Vlock A1 S. Giguère A1 N. D. Cohen A1 G. B. Pier YR 2018 UL http://biorxiv.org/content/early/2018/04/02/292946.1.abstract AB Immune correlates for protection against Mycobacterium tuberculosis (Mtb) infection and other intracellular pathogens are largely undetermined. Whether there is a role for antibody-mediated immunity is controversial. Rhodococcus equi is an intracellular pathogen causing severe pneumonia in young horse foals, eliciting a disease with many similarities to TB including intracellular residence, formation of granulomas and induction of severe respiratory distress. No purified vaccine antigens exist for R. equi or Mtb infections. Both express the microbial surface polysaccharide antigen poly-N-acetyl glucosamine (PNAG). In a randomized, controlled, blinded challenge trial, vaccination of pregnant mares with a synthetic PNAG oligosaccharide conjugated to tetanus toxoid elicited antibody that transferred to foals via colostrum and provided nearly complete protection against R. equi pneumonia. Infusion of PNAG-hyperimmune plasma protected 100% of foals against R. equi pneumonia. Vaccination induced opsonic antibodies that killed extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms was dependent on antibody recognition of surface expression of PNAG on infected macrophages, complement deposition and PMN-assisted lysis of infected macrophages. Protection also correlated with PBMC release of interferon-γ in response to PNAG. Antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against disease caused by intracellular bacterial pathogens.