Key Dates

Related Announcements

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

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

This Notice of Special Interest (NOSI) solicits transdisciplinary research projects to understand 1) the immunologic events in the vertebrate host that occur at the bite site (skin) and systemically during and after feeding by hematophagous and ectoparasitic arthropods and 2) how immunologic events and vector salivary factors influence pathogen transmission and pathogenesis, impact induction or inhibition of protective immune responses, or cause allergic responses.  Exploratory research on immune responses to arthropod blood feeding was formerly supported by the National Institute of Allergy and Infectious Diseases (NIAID) through the expired notice of funding opportunity (NOFO),  PAR-18-860 , “Immune Response to Arthropod Blood Feeding (R21 Clinical Trial Not Allowed), and NOT-AI-21-059 , “Notice of Special Interest (NOSI): Immune Responses to Arthropod Feeding on Vertebrate Hosts.” The intent of this NOSI is to indicate continued NIAID interest for research in this area as described below.

Background

The NIAID supports a broad range of research programs focused on advancing the understanding of immunology, vector biology, and the transmission of vector-borne diseases. Many pathogens are transmitted to humans by arthropod vectors during blood feeding, but the mechanisms and the role of vector factors involved in this process remain unclear. It is known that biologically active molecules presented in arthropod saliva have immunomodulatory effects in the vertebrate host and play a significant role in local and systemic pathogen transmission and pathogenesis during and after blood feeding. Similarly, ectoparasites (e.g., mites, chiggers, bed bugs) can live and multiply in human skin and feed within the skin interface, thereby exposing the vertebrate host to salivary immunomodulatory factors that not only lead to localized inflammation, allergy, or dermatitis, but also indirectly increase the potential for exposure to various viruses, bacteria, and fungi. However, many of the individual salivary components have not yet been identified, and the mechanisms by which they affect pathogen transmission, establishment of infection, or vertebrate host immunity are largely unknown.

Research into vaccines, therapeutics, and diagnostics will benefit from a better understanding of the immune responses triggered by bioactive components in arthropod saliva and how they alter the host immune response. The identification of immunoregulatory salivary factors and elucidation of the underlying mechanism of how the salivary components modulate the host immune system will significantly expand our understanding of the pathogenesis of vector-borne diseases and shed light on the development of novel vaccines and therapeutics to prevent and treat these diseases that affect populations in the United States and globally. This NOSI supports studies to better understand the role of arthropod salivary factors in the establishment of vector-borne infections and immune-mediated diseases (e.g., alpha-gal syndrome) and local as well as systemic immune modulation. In addition, the NOSI supports the NIAID Pandemic Preparedness Plan, the NIH Strategic Plan for Tickborne Disease Research (Objectives 1.3 and 1.4), and the National Public Health Strategy to Prevent and Control Vector-borne Diseases in People.

Research Objectives

The purpose of this NOSI is to encourage multidisciplinary research to understand the immunologic events and/or introduction of vector salivary factor in the vertebrate host at the bite site and systemically during and after feeding by hematophagous (e.g., mosquitoes, ticks) and ectoparasitic (e.g., mites, chiggers, bed bugs) arthropods that influence pathogen transmission and pathogenesis, impact induction or inhibition of protective immune responses, or cause allergic responses. Another goal of this NOSI is to foster new and/or strengthen existing collaborations between vector biologists and immunologists.

The scientific objectives of this NOSI are to:

• Understand the events in the vertebrate host at the bite site (skin) and systemically that occur during and after feeding by hematophagous and ectoparasitic arthropods that influence pathogen transmission and pathogenesis;
• Identify and characterize arthropod salivary components that exhibit immune modulatory properties;
• Determine the factors and mechanisms responsible for induction of protective immunity or allergic disease (i.e., alpha-gal syndrome or dermatitis) triggered by hematophagous or ectoparasitic arthropods;
• Explore the utility of newly discovered salivary factors for modulating allergic reactions and host immune responses and/or controlling vector-born pathogen replication and transmission.

Examples of research topics supported by this initiative include, but are not limited to:

• Characterization of the events in the vertebrate host that occur during and after blood feeding by hematophagous and ectoparasitic arthropods that influence pathogen transmission and pathogenesis, at the bite site (skin) and systemically;
• Identification and analysis of salivary factors secreted into vertebrate skin during arthropod feeding and their role in immune modulation. Salivary factors include proteins, RNA, peptides, lipids, nucleosides, small molecules, etc.;
• Determination of the immunological mechanisms that lead to galactose-α-1,3-galactose (alpha-gal) allergy, known as alpha-gal syndrome, in the vertebrate host following a tick bite; and identification of tick salivary factors that contribute to alpha-gal syndrome.
• Examination of the factors and mechanisms that lead to allergic skin responses and dermatitis in the vertebrate host triggered by ectoparasitic arthropods;
• Determination of changes in the immune response and impact on pathogen transmission by targeting specific arthropod salivary factors before, during, and after feeding.

Research areas NOT responsive to this NOSI include:

• Studies which focus solely on the pathogen;
• Studies which do not include a vertebrate host immunological component or do not include studies of vector salivary factors;

Application and Submission Information

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

Submit applications for this initiative using one of the following notice of funding opportunity announcements (NOFOs) 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 Project Grant (Parent R21 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-24-048” (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

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)

Qian “Joy” Liu, M.Sc., MD
Division of Allergy, Immunology, and Transplantation (DAIT)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6621
Email: liujoy@niaid.nih.gov

Adriana Costero Saint-Denis, Ph.D.
Division of Microbiology and Infectious Diseases (DMID)
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-2544
Email: acostero@niaid.nih.gov

Financial/Grants Management Contact(s)

Tamia Powell
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2982
Email: tamia.powell@nih.gov