Notice of Special Interest (NOSI): Inborn Errors of Immunity/Primary Immunodeficiencies
Notice Number:

Key Dates

Release Date:

March 20, 2024

First Available Due Date:
June 05, 2024
Expiration Date:
March 17, 2027

Related Announcements

March 20, 2024 - Notice of Special Interest (NOSI): Inborn Errors of Immunity/Primary Immunodeficiencies. See Notice NOT-AI-24-026

May 05, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185
May 07, 2020 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed). See NOFO PA-20-195
May 07, 2020 - NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed). See NOFO PA-20-200

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)


The purpose of this Notice of Special Interest (NOSI) is to support research on the discovery and characterization of Inborn Errors of Immunity (IEIs), also referred to as Primary Immunodeficiencies, to understand the causes and mechanisms of disease, enable early detection and molecular diagnosis, and support the development of strategies to treat and eventually cure these disorders.

Innovations in whole genome sequencing and other high throughput technologies have led to more rapid discovery of novel genes and molecular pathways responsible for aberrant or sub-optimal immune responses, leading to enhancement of infection or other immune-mediated diseases.  Identification of genes and pathways associated with IEIs should inform discovery and development of novel diagnostic methods to inform personalized approaches for therapies.

This NOSI will support research on the following topics of IEIs:

  • Combined immunodeficiencies with associated or syndromic features
  • Diseases of immune dysregulation
  • Congenital defects of phagocyte number or function
  • Defects in intrinsic and innate immunity
  • Immunodeficiencies affecting adaptive immunity
  • Autoinflammatory disorders
  • Complement deficiencies
  • Bone marrow failure

Research areas supported by this NOSI include, but are NOT limited to:

  • Identifying the genetic basis of IEIs (single nucleotide variants, indels, digenic/polygenic structural variations).
  • Characterizing the contribution of modifier genes in the pathogenesis of IEIs.
  • Validating genetic variants and/or mutations causing IEIs.
  • Developing novel strategies or refining existing strategies to treat and ultimately cure IEIs.
  • Developing in vitro and in vivo models to study IEIs, including models to test therapeutic strategies.
  • Characterizing the factors that contribute to variable clinical penetrance associated with IEIs.
  • Characterizing the factors that contribute to phenotypic diversity associated with IEIs.
  • Developing consistent, systematic approaches to annotate IEIs.
  • Elucidating the mechanisms of immune dysregulation that result in non-infectious complications in IEIs.
  • Investigating the role of the gut microbiome in the pathogenesis of IEIs.
  • Investigating genotype-phenotype correlations among IEIs.
  • Investigating the factors responsible for age-related complications associated with IEIs.
  • Discovering/developing improved diagnostic/newborn screening tools for IEIs.
  • Discovering biomarkers to aid in disease profiling, disease progression, prediction of adverse effects to therapy etc., for IEIs.
  • Analyzing clinical data and samples maintained in primary immunodeficiency registries, consortium databases, and repositories to address questions relevant to IEI research.

This NOSI will NOT support research in the following topic areas:

  • Immunodeficiency resulting from infection (e.g., HIV)
  • Immunodeficiency resulting from treatments (e.g., chemotherapy), exposures (e.g., radiation), immunosuppression following transplantation, or autoimmune disorders not associated with inborn errors of immunity
  • Immunodeficiency resulting from aging or immaturity
  • Characterization of somatic mutations
  • Phenocopies of inborn errors of immunity/primary immunodeficiency diseases
  • Basic immunologic mechanisms unless directly related to the understanding of inborn errors of immunity

Applications proposing NIH-defined clinical trials will be considered non-responsive to this NOSI.  However, use of human samples, including those from independently supported clinical trials, is welcomed and encouraged. For any questions concerning this NOSI, applicants are encouraged to communicate with the Scientific/Research contact listed below.

Application and Submission Information

This notice applies to due dates on or after June 5, 2024 and subsequent receipt dates through March 16, 2027.

Submit applications for this initiative using one of the following NOFO or any reissues of these announcements through the expiration date of this notice.

  • PA-20-185 – NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
  • PA-20-195 – NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
  • PA-20-200 – NIH Small Research Grant Program (Parent R03 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-AI-24-024” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Maggie A. Morris Fears, PhD
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444

Financial/Grants Management Contact(s)

Tamia Powell
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240.669.2982