NIH Characterisation of Mycobacterial Induced Immunity in HIV-infected and Uninfected Individuals, 2020

Open date: 14 Dec 2018

Deadline for applications: 14 Jan 2020

 

Purpose

This Funding Opportunity Announcement (FOA) encourages applications that will provide new insights into the immune mechanisms required for protection from Mycobacterium tuberculosis (Mtb) infection or progression to active disease in latently infected individuals. Studies may focus on any mycobacterial infection stage, i.e., the full spectrum of latent infection and active disease, or on responses following vaccination with Bacillus Calmette-Guérin (BCG) or investigational vaccines in latently infected persons or uninfected persons and may include HIV-infected or uninfected individuals. Analysis of clinical samples evaluating tuberculosis (TB) vaccine candidates to identify immune correlates of protection or disease progression are encouraged. Applications are sought that propose: 1) Development of novel functional assays to assess the host immune response against mycobacterial infections or candidate vaccines; 2) characterization of the timing, anatomical location, and contribution to disease outcome of systemic and mucosal immune responses to mycobacterial infection and/or vaccination; 3) monitoring of immune responses in appropriate animal models during preclinical studies and vaccine candidate selection. Use of systems biology and immune profiling approaches are encouraged. The outcomes of these research projects are expected to provide the foundation for new hypotheses that can contribute to the advancement of the next generation of TB vaccines.

 

Objectives and Scope

The goal of this announcement is to encourage innovative studies to identify and understand the immunological responses that mediate protection from Mtb infection or progression to active disease, or following vaccination with BCG or investigational vaccines. Proposed studies may focus on any mycobacterial infection stage and may or may not include HIV-infected individuals. Studies with human cells and tissues are encouraged and can include samples from both HIV-infected or -uninfected individuals. Studies involving human biospecimens/data may use samples collected from previous clinical trials or new samples to be collected from future or ongoing clinical trials that are funded by other mechanisms/sponsors. Research using well-justified animal models is acceptable. Animal model development is allowed only when the goals clearly indicate which aspects of human/pathogen interaction are modeled.

Specific research areas of interest include, but are not limited to:
 

  • Development of novel functional assays (and development of associated required reagents) to assess the host immune response against mycobacterial infections or candidate vaccines to increase information output and/or significantly minimize the amount of samples needed for a given evaluation.
  • Elucidation of mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms, throughout the course of mycobacterial infection/disease or vaccination.
  • Analysis of clinical trial samples evaluating TB vaccine candidates to identify immune correlates of protection from Mtb infection, or TB disease progression.
  • Analysis of innate immune pathways and mechanisms in response to Mtb infection and/or TB progression, including trained immunity and the effect on down-stream activation of adaptive immune responses.
  • Application of systems immunology approaches for analysis of systemic and tissue-specific responses to Mtb, BCG or investigational vaccines.
  • Effect of prior/chronic exposure to mycobacterial species (including nontuberculous mycobacteria), or BCG vaccination, or other TB vaccine candidates on subsequent immune responses to Mtb infection, TB reactivation, or disease reoccurrence in HIV-infected or uninfected individuals.
     

Applications proposing the following research topics will NOT be supported under this FOA:
 

  • Projects that focus solely on mechanisms of TB pathogenesis that do not include analysis of immune parameters.
  • Projects that focus specifically/primarily on reagent or animal model development. 

 

For more information, or to apply, visit the call webpage.