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 equiis 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. equior 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. equipneumonia. Infusion of PNAG-hyperimmune plasma protected 100% of foals against R. equipneumonia. Vaccination induced opsonic antibodies that killed extracellular and intracellular R. equiand 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- in response to PNAG. Antibody-mediated opsonic killing and interferon- release in response to PNAG may protect against disease caused by intracellular bacterial pathogens.