Effective protection against secondary Mycobacterium tuberculosis challenge with heterologous strain 2503

Abstract Description Background Concomitant immunity, or protection from pre-existing infection, has been estimated to be up to 80% effective in humans by meta-analyses. Our lab previously recapitulated this phenomenon in non-human primates. Here, we used this reinfection model to probe whether protection can be extended to a heterologous Mtb challenge. Methods Eight Indonesian cynomolgus macaques (ICM) were intrabronchially challenged with a Lineage 4 strain of genetically barcoded Mtb (Erdman). This infection was eliminated with standard antibiotics before these ICMs, plus a naïve control group (n = 6), were subsequently challenged with a distinct barcoded strain of Mtb, the Lineage 2 Peruvian clinical isolate referred to as G2G. Serial PET CT scans, bronchoalveolar lavages, and blood draws were performed to track disease progression. Individual granulomas, uninvolved lung lobes, and lymph nodes were excised at necropsy for histological and immunological assays. Results ICMs previously exposed to Erdman developed significantly less disease following G2G challenge and had significantly lower bacterial burden attributable to the secondary infection. These data suggest a robust mechanism conferring cross-lineage immunity – an important consideration as global interconnectivity continues to increase. Our results demonstrate that prior infection can protect against heterologous challenges and provide an opportunity to identify cross-protective mechanisms that will inform future vaccine design. Funding Sources NIH IMPAcTB (HI-IMPACT); NIH T32 5T32AI060525 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)