Innate immune vaccination as a novel approach to promote recovery and prevent infection after spinal cord injury
Funded in: 2019, 2020, 2021, 2022
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Problem: SCI patients develop and die often of pneumonia
Target: Boost the pathogen-killing ability of innate immune system
Goal: Treatments against infection that improve rehabilitation and spontaneous neurological recovery
People with spinal cord injury (SCI) develop and die of pneumonia more often than able-bodied individuals. Since SCI-associated pneumonia (SCI-AP) predicts poorer neurological recovery after SCI, new treatments that fight infection should improve rehabilitation and spontaneous neurological recovery.
In mice and humans, high level SCIs disrupt normal sympathetic nervous system control of all major immune organs, causing a SCI-induced immune depression syndrome (SCI-IDS) marked by the prominent and long-lasting inability of B and T lymphocytes to fight infection. Thus, novel approaches are needed to boost the pathogen-killing ability of other immune cells. Doing so may prevent pneumonia and improve recovery.
Recently, it was discovered that vaccines can “train” innate immune cells (e.g., macrophages, dendritic cells), endowing them with enhanced and long-lasting (memory) bactericidal functions.
Two important aspects of innate immune training are relevant to SCI:
(1) training does not require T and B cells and
(2) trained innate immune cells can protect against diverse pathogens, even those not present in the original vaccine.
Long-lasting “innate immune memory” may also confer neuroprotection.
Pilot data from the lab show that boosting innate immunity with microbial inoculations can limit ischemic SCI. The BCG vaccine is one of the world’s safest and most widely used vaccines. Although primarily used to protect against tuberculosis (TB), new data show that BCG vaccines also can prevent recurring bladder cancers, treat melanoma and protect against influenza.
BCG is also effective in reducing respiratory infections, including pneumonia, thus, it may also prove useful as a novel multi-modal treatment for SCI individuals. Using mouse models of SCI, the scientists will test whether BCG and other innate immune vaccines can enhance pulmonary immune surveillance to block spontaneous or experimental pneumonia. Optimized vaccines will also be tested for their ability to elicit neuroprotective intraspinal inflammation.