Notice Number: NOT-AI-17-003

Key Dates
Release Date: October 21, 2016

Issued by
National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

The purpose of this Notice is to inform potential applicants of additions to the Objectives and Scope section of PAR-16-254, "Mechanisms of Mycobacterial-Induced Immunity in HIV-Infected and Uninfected Individuals to Inform Innovative Tuberculosis Vaccine Design (R01)".

Part 2. Section I. Funding Opportunity Description

Objectives and Scope

Current Language:

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

• Elucidation of mechanisms (host or pathogen) responsible for transition to active TB disease in susceptible individuals and how HIV infection may shift this balance
• Understanding how Mtb infection, BCG, or investigational vaccines influence specific cellular signaling pathways and/or cause epigenetic changes that impair immune cell functions to prevent or reverse infection, persistence, or reactivation
• Effect of prior/chronic exposure to NTM, BCG vaccination, or candidate Mtb vaccines on subsequent immune responses to Mtb infection, TB reactivation, or disease reoccurrence in HIV-infected or HIV-uninfected individuals
• Identification and analysis of immune responses elicited during Mtb infection in either HIV-infected or HIV-uninfected people, including:
  • Immune responses that may benefit mycobacterial persistence
  • Innate immune pathways and mechanisms, such as the effect of Mtb infection on innate immune cell function and down-stream activation of adaptive immune responses
  • Mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms triggered by mycobacterial infection/disease
  • Role of non-classical T cells in immunity to Mtb infection
• The contribution of the humoral immune response to protection against Mtb or immune evasion by Mtb
• Effect of Mtb or related mycobacteria infection of thymic epithelial cells on local or systemic host immune responses to Mtb infection or candidate vaccines, such as the induction of immune tolerance to mycobacterial antigens
• Identification of processes associated with how protective immune cells can be mobilized to, and maintained in, the lung
• Mechanisms governing Mtb-induced decoy immune responses and their implications for vaccine design
• Investigation of the timing/nature of immune responses leading to protection against disseminated TB in children to determine whether activity of BCG can be modified to protect adults against Mtb infection or disease
• Studies to determine the function of specific vaccine adjuvants on immunity to Mtb infection

Note: Projects that use animal models, including the SIV/Mtb co-infection model, may be considered through this FOA to address FOA objectives.

Revised Language:

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

• Understanding the functional capacity of innate and adaptive immune responses in the lung and granuloma microenvironments
• Elucidation of mechanisms (host or pathogen) responsible for transition to active TB disease in susceptible individuals and how HIV infection may shift this balance
• Understanding how Mtb infection, BCG, or investigational vaccines influence specific cellular signaling pathways and/or cause epigenetic changes that impair immune cell functions to prevent or reverse infection, persistence, or reactivation
• Effect of prior/chronic exposure to NTM, BCG vaccination, or candidate Mtb vaccines on subsequent immune responses to Mtb infection, TB reactivation, or disease reoccurrence in HIV-infected or HIV-uninfected individuals
• Identification and analysis of immune responses elicited during Mtb infection in either HIV-infected or HIV-uninfected people, including:
  • Immune responses that may benefit mycobacterial persistence
  • Innate immune pathways and mechanisms, such as the effect of Mtb infection on innate immune cell function and down-stream activation of adaptive immune responses
  • Mucosal and systemic adaptive immune responses, including signaling networks and regulatory mechanisms triggered by mycobacterial infection/disease
  • Role of non-classical T cells in immunity to Mtb infection
• The contribution of the humoral immune response to protection against Mtb or immune evasion by Mtb
• Understanding the role of innate and non-immune cells in lung mucosal surveillance and the development of mucosal effector and regulatory immune pathways
• Identification of lung mucosal immune responses that reflect or contrast with systemic responses
• Effect of Mtb or related mycobacteria infection of thymic epithelial cells on local or systemic host immune responses to Mtb infection or candidate vaccines, such as the induction of immune tolerance to mycobacterial antigens
• Identification of processes associated with how protective immune cells can be mobilized to, and maintained in, the lung
• Mechanisms governing Mtb-induced decoy immune responses and their implications for vaccine design
• Investigation of the timing/nature of immune responses leading to protection against disseminated TB in children to determine whether activity of BCG can be modified to protect adults against Mtb infection or disease
• Studies to determine the function of specific vaccine adjuvants on immunity to Mtb infection

Note: Projects that use animal models, including the SIV/Mtb co-infection model, may be considered through this FOA to address FOA objectives.

All other aspects of the FOA remain the same.

Inquiries

Please direct all inquiries to:

Cesar Boggiano, PhD
Division of AIDS
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3038
Email: cesar.boggiano@nih.gov

Katrin Eichelberg, PhD
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2921
Email: keichelberg@niaid.nih.gov

Alison Deckhut Augustine, PhD
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-627-3475
Email: augustine@niaid.nih.gov