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Related Announcements

NOT-AI-24-024 - Notice of Special Interest (NOSI): Inborn Errors of Immunity/Primary Immunodeficiencies.

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)

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

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

Inborn Errors of Immunity/Primary Immunodeficiencies result largely from inherited genetic defects that perturb immune regulation or function; they are often severe in nature; and are characterized by highly diverse phenotypes such as infection, autoimmunity, auto-inflammation, allergy, and/or malignancy. More than 400 Inborn errors of immunity have been identified, as noted by the International Union of Immunological Societies (IUIS) Expert Committee: 2019 update on the classification of Inborn Errors of Immunity , and this number is expected to rise. The global prevalence of inborn errors of immunity is estimated to be at least 1:1000 to 1:5000 live births and for some inborn errors of immunity the prevalence is even higher. Identification of the causes and pathogenesis of inborn errors of immunity has provided important insights into the fundamental mechanisms of human immunity and contributed to the understanding of a wide range of human diseases and the development of immunotherapies. There are numerous examples that illustrate the contribution of inborn errors of immunity research in the elucidation of human immune mechanisms. Specifically, the discovery that loss-of-function mutations in the transcription factor ZNF341 cause an autosomal recessive form of hyper-IgE syndrome, typically caused by autosomal dominant mutations in STAT3, revealed a novel mechanism of regulating STAT3 signaling via the ZNF341 transcription factor and further defined the phenotypes of autosomal dominant hyper-IgE syndrome. Furthermore, the molecular characterization of inborn errors of immunity leads to improved patient management in the clinic, through the use of gene-specific therapies (e.g., JAK inhibitors, mTOR inhibitors/rapamycin, CTLA4-Ig/abatacept etc).

Research Objectives and Scope

This NOSI will support investigations on inborn errors of immunity/primary immunodeficiencies classified by the IUIS as follows:

• Immunodeficiencies affecting cellular and humoral immunity;
• Combined immunodeficiencies with associated or syndromic features;
• Predominantly antibody deficiencies;
• Diseases of immune dysregulation;
• Congenital defects of phagocyte number or function;
• Defects in intrinsic and innate 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 inborn errors of immunity;
• Characterizing the contribution of modifier genes in the pathogenesis of inborn errors of immunity;
• Developing novel strategies or refining existing strategies to treat and ultimately cure inborn errors of immunity;
• Developing in vitro and in vivo models to study inborn errors of immunity including models to test therapeutic strategies;
• Characterizing the factors that contribute to variable clinical penetrance associated with inborn errors of immunity;
• Characterizing the factors that contribute to phenotypic diversity associated with inborn errors of immunity;
• Developing consistent, systematic approaches to annotate inborn errors of immunity;
• Elucidating the mechanisms of immune dysregulation that result in non-infectious complications in inborn errors of immunity;
• Investigating the role of gut microbiome in the pathogenesis of inborn errors of immunity;
• Investigating genotype-phenotype correlations among inborn errors of immunity;
• Investigating the factors responsible for age-related complications associated with inborn errors of immunity;
• Discovering/developing improved diagnostic/newborn screening tools for inborn errors of immunity;
• Discovering biomarkers to aid in disease profiling, disease progression, prediction of adverse effects to therapy etc., for inborn errors of immunity;
• Analyzing clinical data and samples maintained in primary immunodeficiency registries, consortium databases, and repositories to address questions relevant to inborn errors of immunity research.

Applications Not Responsive to this NOSI:

• 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;
• Basic immunologic mechanisms unless directly related to the understanding of inborn errors of immunity.

This NOSI will NOT accept clinical trials. However, studies using human samples are encouraged if they are within the research objectives and scope of the NOSI, and if they do not involve clinical intervention. Studies using human samples obtained from ongoing clinical trials supported outside this NOSI will be considered for funding as well. 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, 2021 and subsequent receipt dates through May 7, 2024.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement 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 theSF424 (R&R) Application Guideand the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-AI-21-032 (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.

Inquiries

Scientific/Research Contact(s)

Maggie A. Morris Fears, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-5444
Email: maggie.morrisfears@nih.gov