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LB19. Intramuscular therapeutic immunization targeting RelMtb/MIP-3 induces immune signatures associated with better TB control in vivo compared to

LB19. Intramuscular therapeutic immunization targeting RelMtb/MIP-3 induces immune signatures... Conclusion. Population rates of ARI visits and relative proportions of ARI vs. non vitro and in animal lungs. Recently, our group has generated a therapeutic, parenteral, ARI visits differed between racial/ethnic groups by setting. Understanding how utilization relMtb DNA vaccine, which induces Rel -specific cellular immunity and augments Mtb of care varies for ARI across settings can inform future monitoring efforts for health equity. the activity of the first-line drug isoniazid against active TB in mice and guinea pigs. Disclosures. All Authors: No reported disclosures Our group also has applied a novel vaccination strategy involving the fusion of an antigen of interest with the immature dendritic cell (iDC)-targeting chemokine MIP-3α/CCL20, which significantly enhances antigen-specific T-cell responses. We LB19. Intramuscular therapeutic immunization targeting Rel /MIP-3 induces Mtb sought to determine if this iDC-targeting strategy improves the immunogenicity of the immune signatures associated with better TB control in vivo compared to 1 2 3 therapeutic relMtb DNA vaccine. Styliani Karanika, MD ; James Gordy, PhD ; Pranita Neupane, MD ; 2 4 1 Methods. We cloned the relMtb and chemokine MIP-3α genes into the eukary- Richard Markham, MD ; Petros Karakousis, MD ; e J Th ohns Hopkins Hospital, 2 otic expression plasmid pSectag2b. We conducted an immunogenicity study using Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, 3 C57BL/6J mice, comparing the T-cell responses between the relMtb vs. MIP-3α/relMtb Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland; 4 DNA intramuscular vaccination groups. Center for Tuberculosis Research, Department of Medicine, Johns Hopkins Results. Intramuscular administration of the DNA vaccine expressing the University School of Medicine, Baltimore, Maryland MIP-3α/relMtb gene fusion induced increased production of various Mtb-protective Session: 132. Late Breaker Abstracts cytokines (IL-17α, IL-2, TNF-α, IFN-γ) in various mouse tissues, including the spleen, Saturday, October 2, 2021: 1:15 PM draining lymph nodes and peripheral blood mononuclear cells, relative to the vaccine expressing relMtb alone. Background. Tuberculosis (TB) is one of the leading causes of death from a single Conclusion. Intramuscular immunization with a DNA vaccine expressing infectious agent worldwide. The lengthy treatment regimen reflects the unique ability relMtb/MIP-3α induces robust in vivo Mtb-protective immune signatures, suggesting of a subpopulation of “persister” bacteria to remain in a nonreplicating state in the this may be a promising adjunctive approach in combination with standard anti-TB infected host through various adaptive strategies, including induction of the strin- therapy. gent response. The key stringent response enzyme, Rel , is essential for long-term Mtb Disclosures. All Authors: No reported disclosures Mycobacterium tuberculosis (Mtb) survival under physiologically relevant stresses in Late Breaking Abstracts • OFID 2021:8 (Suppl 1) • S815 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Oxford University Press

LB19. Intramuscular therapeutic immunization targeting RelMtb/MIP-3 induces immune signatures associated with better TB control in vivo compared to

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Publisher
Oxford University Press
Copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
eISSN
2328-8957
DOI
10.1093/ofid/ofab466.1655
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Abstract

Conclusion. Population rates of ARI visits and relative proportions of ARI vs. non vitro and in animal lungs. Recently, our group has generated a therapeutic, parenteral, ARI visits differed between racial/ethnic groups by setting. Understanding how utilization relMtb DNA vaccine, which induces Rel -specific cellular immunity and augments Mtb of care varies for ARI across settings can inform future monitoring efforts for health equity. the activity of the first-line drug isoniazid against active TB in mice and guinea pigs. Disclosures. All Authors: No reported disclosures Our group also has applied a novel vaccination strategy involving the fusion of an antigen of interest with the immature dendritic cell (iDC)-targeting chemokine MIP-3α/CCL20, which significantly enhances antigen-specific T-cell responses. We LB19. Intramuscular therapeutic immunization targeting Rel /MIP-3 induces Mtb sought to determine if this iDC-targeting strategy improves the immunogenicity of the immune signatures associated with better TB control in vivo compared to 1 2 3 therapeutic relMtb DNA vaccine. Styliani Karanika, MD ; James Gordy, PhD ; Pranita Neupane, MD ; 2 4 1 Methods. We cloned the relMtb and chemokine MIP-3α genes into the eukary- Richard Markham, MD ; Petros Karakousis, MD ; e J Th ohns Hopkins Hospital, 2 otic expression plasmid pSectag2b. We conducted an immunogenicity study using Baltimore, MD; Johns Hopkins Bloomberg School of Public Health, Baltimore, 3 C57BL/6J mice, comparing the T-cell responses between the relMtb vs. MIP-3α/relMtb Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland; 4 DNA intramuscular vaccination groups. Center for Tuberculosis Research, Department of Medicine, Johns Hopkins Results. Intramuscular administration of the DNA vaccine expressing the University School of Medicine, Baltimore, Maryland MIP-3α/relMtb gene fusion induced increased production of various Mtb-protective Session: 132. Late Breaker Abstracts cytokines (IL-17α, IL-2, TNF-α, IFN-γ) in various mouse tissues, including the spleen, Saturday, October 2, 2021: 1:15 PM draining lymph nodes and peripheral blood mononuclear cells, relative to the vaccine expressing relMtb alone. Background. Tuberculosis (TB) is one of the leading causes of death from a single Conclusion. Intramuscular immunization with a DNA vaccine expressing infectious agent worldwide. The lengthy treatment regimen reflects the unique ability relMtb/MIP-3α induces robust in vivo Mtb-protective immune signatures, suggesting of a subpopulation of “persister” bacteria to remain in a nonreplicating state in the this may be a promising adjunctive approach in combination with standard anti-TB infected host through various adaptive strategies, including induction of the strin- therapy. gent response. The key stringent response enzyme, Rel , is essential for long-term Mtb Disclosures. All Authors: No reported disclosures Mycobacterium tuberculosis (Mtb) survival under physiologically relevant stresses in Late Breaking Abstracts • OFID 2021:8 (Suppl 1) • S815

Journal

Open Forum Infectious Diseases – Oxford University Press

Published: Dec 4, 2021

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