Posted: March 13, 2020

Letter of Intent due 30 days prior to application; Application due July 28, 2020

The product profile of an ideal therapeutic vaccine for TB is unknown and requires further investigation. Additionally, using adjunctive host-directed therapies designed to modulate relevant immune cell regulatory pathways in order to compliment vaccination remains to be explored.

The goal of this Funding Opportunity Announcement is to encourage innovative studies focused on:

  • Correlating changes in host immune cell regulation and functions associated with Mtb proliferation versus control during active infection and/or clinical recurrence.
  • Assessing the effects of candidate TB vaccines and adjuvants combined with TB antimicrobial therapy (and HIV-ART, as appropriate) for drug-sensitive and drug-resistant TB on responses related to treatment outcomes.
  • Evaluating the impact of Mtb strain variation and host genetic/epigenetic factors on immune responses to candidate therapeutic vaccines and adjuvants and modulation of disease outcomes, i.e., decreasing recurrence and/or treatment shortening.

Areas of Research Interest

Research topics of interest in advancing therapeutic vaccine science for improving TB treatment outcomes in the presence or absence of HIV include, but are not limited to:

  • Identifying mechanisms of immune alterations during active disease and in relapse settings with focus on enhancing effective immunity and/or restricting immune suppression
  • Understanding changes in immune cell regulatory pathways, metabolism, gene expression, and epigenetics as targets for therapeutic vaccine/adjuvant design
  • Investigating Mtb microbial factors involved in immune-suppressive responses
  • Evaluating current and novel candidate TB vaccines/adjuvants with antimicrobial chemotherapy (including for drug-sensitive/multi-drug resistant TB and, as appropriate, HIV ART) for decreasing recurrence and/or treatment shortening strategies
  • Rational design of vaccines with adjuvants/host-directed therapy agents to enhance or restrict specific immune responses and improve therapeutic outcomes
  • Assessing the impact of vaccination timing during and/or after TB therapy
  • Assessing effects of therapeutic vaccination for potential changes in tissue damage
  • Identification of correlates of protection from TB recurrence and potentially a biosignature for protection status in the context of vaccine intervention

Studies with appropriate animal models and human cells and tissues are encouraged and may include samples from both HIV-infected and uninfected individuals. Animal model adaption/improvement and development of novel functional assays for correlating changes in immune functions with treatment effects is encouraged but cannot be a primary focus of the application.

Collaborative multidisciplinary research teams incorporating expertise in infectious disease, vaccinology, and immunology and utilizing research tools novel to the infectious disease field to probe molecular targets and alterations in specific host defense mechanisms triggered by TB disease and vaccines/adjuvants are strongly encouraged.

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