Investigating the mechanisms of influenza virus group-level imprinting
Active Project Grant Awarded Last action
- Award ID
- F31AI197754
- Recipient
-
The Regents Of The University Of Colorado UEI MW8JHK6ZYEX8 Part of The Regents Of The University Of Colorado
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $77,596
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Originally
- Place of performance
- Aurora, CO 80045, USA
Award details come from USAspending.gov.
Description
- Abstract
- Influenza a viruses (IAVS) remain a significant global health threat, largely due to antigenic variability within the hemagglutinin (HA) protein. HA is divided into two phylogenetic groups, with the initial infection creating a lifelong immunological 'imprinting' bias viruses possessing has within the same group. The mechanisms that govern group-level imprinting biases are poorly understood. Understanding the mechanisms driving group-level imprinting biases is required for the development of therapeutics that extend group-level protection against infection to all individuals, regardless of their imprinting strain and exposure history. The overall goal of this proposal is to determine how group-level imprinting biases are generated and maintained. To determine how group-level imprinting biases are generated and maintained, we must first understand the antigenic context in which they are elicited. Our preliminary data show that the imprinting IAV infection preferentially promotes humoral immunity against has belonging to the imprinting group upon immunizations containing drifted group 1 and group 2 has, suggesting a role for recalled imprinting-derived mbcs as antigenic distance increases. Further, our data suggest that preexisting antibodies form HA-immune complexes (HA-ICS) that bias the HA group specificity of subsequent responses. I hypothesize that imprinting-derived mbcs and preexisting antibodies act synergistically to bias subsequent humoral responses towards has within the same phylogenetic group. The experiments proposed in aim 1 will define the role of antigenic distance on the reactivation, differentiation, and HA specificity of imprinting-derived mbcs. In aim 2, we will further investigate the role of antigenic distance on HA-IC formation and determine if imprinting-derived antibodies bias subsequent humoral responses towards phylogenetically similar has through HA-ICS. The results of the proposed experiments will define whether increased antigenic distance between the imprinting and secondary HA promotes imprinting- derived mbcs to RE-enter the GC upon reactivation and bias the HA specificity of germinal center B cells. Additionally, these results define whether HA-ICS are mechanistically relevant in reinforcing group-level imprinting biases. The findings generated by this proposal will be foundational to our understanding of how imprinted humoral responses are recalled and generated against antigenically distant has, such as those present in zoonotic IAVS.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,798 | |
| Amendment | $0 | |
| Original award | $38,798 |
Quick answers
Who received award F31AI197754?
F31AI197754 was awarded to The Regents Of The University Of Colorado by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on December 4, 2026.
How much is award F31AI197754 worth?
$77,596 has been obligated on F31AI197754.
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