Key Dates

Related Announcements

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)

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

This Notice of Special Interest (NOSI) solicits transdisciplinary research projects to understand 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. Exploratory research on arthropod blood feeding was formerly supported by NIAID through the expired FOA, PAR-18-860, “Immune Response to Arthropod Blood Feeding (R21 Clinical Trial Not Allowed). The intent of this NOSI is to indicate continued NIAID support for research in this area as described below through applications to the parent R01 and R21 FOAs.

Background

The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), promotes and supports a broad range of research programs focused on advancing the understanding of immunology, vector biology, and transmission of vector-borne pathogens.A large number of pathogens are transmitted to humans by arthropod vectors, but how these pathogens are transmitted from arthropod vectors to vertebrate hosts is not well-defined. A common feature shared among hematophagous arthropod vectors during blood feeding is the exchange of biologically active molecules and microbiota between the arthropod and the vertebrate host at the bite site. During this process, the arthropod releases salivary factors into the vertebrate host skin and ingests vertebrate bioactive molecules.It is well-established that arthropod salivary factors have immunomodulatory effects in the vertebrate host and play a significant role in pathogen transmission and pathogenesis. Similarly, although ectoparasites (e.g., mites, chiggers, bed bugs) may not transmit pathogens, they can live and multiply in human skin, and feed within the skin interface, thereby exposing the vertebrate host to salivary immunomodulatory factors, which not only lead to localized inflammation, allergy, dermatitis, or vein eruptions, but also indirectly increase the transmission of various viruses and bacteria. However, few of these salivary immunomodulatory and immunosuppressive molecules have been characterized in select arthropod vectors. Many of the individual salivary components have not yet been identified and the mechanisms by which they act on the vertebrate host are largely unknown. Research on the identification of immunoregulatory salivary factors and elucidation of the underlying mechanism of how the salivary components modulate the 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. In addition, the recent increase in allergic responses to red meat and other animal-derived products following tick bites has highlighted the importance of the interplay between arthropod-derived salivary factors and the vertebrate host’s immune system. Thus, 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. This NOSI supports the NIH Strategic Plan for Tickborne Disease Research (objective 1.3.: alpha-gal syndrome, 1.4.: study of salivary proteins).

In addition to addressing the immediate scientific objectives, studies in response to this NOSI will have broader implication. Identification and characterization of novel immunologically active molecules from blood-feeding arthropods could lead to the identification of new vaccine adjuvants, therapeutic drugs for the treatment of inflammation or autoimmune disease, or new antigenic targets for the development of vaccines against arthropod saliva or as biomarkers of exposure to vector bite.

Research Objectives

The purpose of this NOSI is to encourage transdisciplinary research to understand the immunologic events in the vertebrate host that occur during and after feeding by hematophagous (e.g., mosquitoes, ticks) and ectoparasitic (e.g., mites, chiggers, bed bugs) arthropods at the bite site and systemically.Given current knowledge gaps, some research areas may involve or require descriptive projects. 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 initiative are to:

• Understand the immunological events in the vertebrate host that occur during and after feeding by hematophagous and ectoparasitic arthropods at the bite site (skin) and systemically;
• Identify and characterize arthropod salivary components that exhibit immune modulatory properties;
• Determine the factors and mechanisms responsible for immune mediated disease (allergy such as alpha-gal syndrome or dermatitis) triggered by hematophagous or ectoparasitic arthropods.

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

• Characterization of the immunologic events in the vertebrate host, which occur during and after blood feeding by hematophagous and ectoparasitic arthropods, at the bite site (skin) and systemically;
• Identification and analysis of salivary factors secreted into vertebrate skin during feedingand 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 (alpha-gal syndrome) in the vertebrate host following a tick bite;
• Examination of the factors and mechanisms that lead to allergic skin responses and dermatitis in the vertebrate host triggered by ectoparasitic arthropods.

Research areas NOT responsive to this NOSI include:

• Studies which focus solely on the pathogen;
• Studies which do not include an immunological component from the vertebrate host;
• Studies which do not include salivary immunomodulatory component from a hematophagous or ectoparasitic arthropod.

Application and Submission Information

This notice applies to due dates on or after October 5, 2021 and subsequent receipt dates through September 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 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-21-059” (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)

Qian “Joy” Liu, M.D., MSc.
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
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-496-2544
Email: acostero@niaid.nih.gov