Notice of Special Interest (NOSI): Advancing Research Needed to Develop a Universal Influenza Vaccine
Notice Number:

Key Dates

Release Date:

December 13, 2021

First Available Due Date:
February 05, 2022
Expiration Date:
January 08, 2025

Related Announcements

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)

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)


The purpose of this Notice of Special Interest (NOSI) is to support research that contributes to the areas of interest outlined in “A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases.” The proposed research should have clear relevance to the research objectives defined in the strategic plan, which encompasses three major research areas:

  • Improve understanding of transmission, natural history and pathogenesis of influenza virus infection
  • Characterize influenza immunity and correlates of immune protection
  • Support rational design of universal influenza vaccines


While vaccines remain the greatest public health tool to protect against influenza illness and disease, the effectiveness of seasonal influenza vaccine remains suboptimal, ranging between 10% and 60%. Circulating viral strains are difficult to predict and the co-circulation of antigenically drifted strains can potentially lead to vaccine mismatches, lowering overall vaccine effectiveness each season. In addition, viral strains with pandemic potential continue to be isolated from avian species, further underscoring the on-going global threat of influenza to public health. To limit the public health consequences of both seasonal and pandemic influenza, vaccines with broader, more durable protection are needed. NIAID continues to identify efforts for the full implementation of the 2018 Strategic Plan for the Development of a Universal Influenza Vaccine.

Recent advances in influenza virology, immunology, and vaccinology make the development of a “universal” influenza vaccine more feasible than a decade ago, and new technological advances resulting from the ongoing COVID-19 pandemic response efforts have revolutionized vaccine development. By tapping new and growing technological advances, the field is poised to make significant scientific advancements that will enable the development of more broadly protective influenza vaccines.

Research Objectives

The purpose of this NOSI is to continue to foster new and innovative scientific endeavors in all areas defined in the Strategic Plan for the Development of a Universal Influenza Vaccine. Specific areas of research interest include, but are not limited to:

  • Improve understanding of influenza transmission, natural history, and pathogenesis:
    • Expand understanding of influenza transmission, including geographic regions, host factors, physical and environmental factors, and identify targets for improving interventions for disease control
    • Determine the role of anti-HA stem and anti-NA antibodies in prevention of transmission
    • Identify viral and host factors associated with transmission and the severity of influenza
    • Identify immune markers associated with reduced disease severity
    • Determine the role of bacterial or viral co-infections with the severity of influenza disease
    • Precisely characterize circulating influenza viruses
    • Develop and test models predicting the influence of pre-existing immunity on virus evolution to anticipate the next emerging dominant seasonal influenza strain
    • Improve genotypic and phenotypic characterization of circulating viruses associated with adverse clinical outcomes, host immunity, and vaccine failures
  • Identify/characterize immune responses required for protection:
    • Improve understanding of how and when exposure to influenza antigens shapes the subsequent immune response to influenza virus infection and vaccination
    • Characterize immune responses in those with a limited HAI response to infection or to vaccination
    • Determine the interaction of innate and adaptive immunity in the response to influenza infection or vaccination
    • Define the mechanism of broadly protective humoral immunity against influenza, including processes that affect antigenic immunodominance
    • Elucidate mechanisms of protective immunity versus those that ameliorate symptomatic disease
    • Assess tissue-resident (e.g., airway) influenza-specific T cell immunity; compare with circulating influenza-specific T cell responses
    • Elucidate antibody responses to hemagglutinin and neuraminidase and their contribution to immune protection
    • Identify alternative mechanisms of antibody-dependent protection beyond virus neutralization/HAI function
  • Support rational design of universal influenza vaccines:
    • Design new immunogens that elicit broad protection
    • Advance new vaccine approaches into preclinical models that exploit emerging antigen design strategies, novel technologies, and/or platforms
    • Define mechanisms and correlates of vaccine-induced protection
    • Identify vaccine candidate(s) that provide broad protection, superior to the seasonal influenza vaccine, and advance candidates to next phase of testing
    • Test adjuvants and alternative delivery methods to enhance breadth and durability of immunity
  • Develop and utilize systems biology approaches to analyze diverse and multi-scale influenza infection and vaccination data sets
  • Develop/improve animal models and reagents to advance vaccine development

Application and Submission Information

This notice applies to application receipt dates on or after February 5, 2022 and subsequent receipt dates through January 7, 2025.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) 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)

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-22-013” (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 funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Jennifer L. Gordon, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Division of Microbiology and Infectious Diseases
Telephone: 301-761-6805

Kentner Singleton, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Division of Allergy, Immunology, and Transplantation
Telephone: 240-669-5499

Financial/Grants Management Contact(s)

Vandhana Khurana
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 240-669-2966