Allergic reactions to drugs and vaccines are a serious public health concern. For the purpose of this notice of funding opportunity (NOFO), allergic reactions include not only IgE-mediated reactions, but other immune-mediated and largely unpredictable drug and vaccine reactions. Based on data from 2013-2014, each year in the United States there are an estimated 200,000 emergency department visits for adverse events related to antibiotics. In children 5 or younger, antibiotics cause more than half (56%) of estimated emergency department visits for adverse drug events and 82% of these visits are due to allergic reactions. Allergic reactions to antibiotics include immediate life-threatening reactions such as anaphylaxis, severe cutaneous reactions including Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms, and less severe reactions that still limit further use of the drugs. A label of antibiotic allergy leads to the use of alternative, frequently more expensive antibiotics, often with lower efficacy, which may contribute to antibiotic resistance as well as increased mortality and morbidity in hospitalized patients. While allergic reactions to vaccines are less common, the inability to receive a vaccine due to an allergy is problematic to the individual, and the perceived risk of allergic reactions to vaccines contributes to vaccine hesitancy creating a public health issue.

Objectives

The objective of this NOFO is to solicit innovative projects to study the mechanisms and management of vaccine or antibiotic drug allergy (research on allergic responses to anti-viral, anti-fungal and anti-parasitic drugs will also be considered).

The scope of research into antibiotic or vaccine allergic reactions includes, but is not limited to, the following:

IgE-mediated and other mechanisms of immediate allergic antibiotic or vaccine reactions
Non-IgE-mediated urticarial reactions to antibiotics or vaccines
Delayed-type hypersensitivity reactions to antibiotics or vaccines
Severe cutaneous adverse antibiotic or vaccine reactions
Biomarkers to identify people at risk for reaction or to confirm reactions to specific antibiotics or vaccines
Host factors that may predispose to allergic reactions including, but not limited to, host microbiome, genetics, or inflammatory conditions
Mechanisms by which specific infections may increase the risk of an allergic reaction to an antibiotic or vaccine
Immunomodulatory approaches to treating or preventing immunologic adverse antibiotic or vaccine reactions
A secondary objective of this NOFO is to expand the number of investigators working in the field of vaccine and antibiotic drug allergy. Early-stage investigators are encouraged to apply.

UG3/UH3 phase transition and Milestones

This funding opportunity is designed as a two-stage cooperative agreement in which Project Scientists from NIAID will work with the investigative team. It will support projects that are organized into a two-year UG3 phase followed by a three-year UH3 phase. The UG3 phase may include pilot, observational, or hypothesis-generating high-risk projects. Preliminary data may be helpful but are not required. The use of electronic health records to identify potential participants for mechanistic studies is allowed. The use of human samples such as those related to clinically indicated and routinely used interventions or tests is encouraged. The UG3 must include milestones to determine the success of the project at the end of this phase. Milestones may be negotiated or re-negotiated after award as this program includes the flexibility to quickly revise milestones and/or aims within the scope of the original peer-reviewed application. Following the completion of the UG3 phase, NIAID staff will review the progress made and make the determination on whether the project will continue to the UH3 phase. NIAID support for the UH3 is contingent upon progress made during the UG3 phase, meeting the milestones, programmatic priorities, the original UG3/UH3 peer review recommendations, and the availability of funds. Some projects might not transition from the UG3 to the UH3 phase. Projects supported by the UH3 phase are required to be hypothesis driven, mechanistic, and extend the work initiated by the UG3 phase.

Program Director/Principal Investigator (PD/PI) Meeting Attendance

A kick-off meeting and annual meetings will be organized by NIAID to facilitate interactions among recipients to share approaches, data, and methods, with the aim of developing a cadre of dedicated researchers to conduct antibiotic and vaccine allergy and advance mechanistic research. These meetings will convene yearly in the Rockville, Maryland area and will be held in person, though a virtual component will be available to allow broader participation from laboratory members. The PD/PI from each award is expected to attend the kickoff meeting and annual meetings in person.

Applications that propose the following topics will be considered non-responsive and will not be reviewed:

Adverse drug reactions that are predictable and/or related to pharmacologic properties of the drug such as toxicity or overdose
Investigation into drugs that are not antibiotics or vaccines (however research on anti-viral, anti-fungal and anti-parasitic drugs is allowed)
Investigations into Guillain-Barré Syndrome or drug-induced autoimmune reactions
Investigations of central nervous system and other neurologic adverse responses
Investigations into the pathogens rather than host allergic responses to the antibiotics or vaccines
Applications that do not propose mechanistic research in the UH3 phase
Vaccines that are administered via a route that is not the same route of administration as approved by the FDA
Vaccines that are used as an immunotherapeutic (e.g. allergen immunotherapy)
HIV/AIDS research