Age-dependent mechanisms of B cell regulation and maturation following HIV sosip vaccination
Active Project Grant Awarded Last action
- Award ID
- F31AI203596
- Recipient
-
Weill Medical College Of Cornell University UEI YNT8TCJH8FQ8
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $50,114
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Place of performance
- New York, NY 10065, USA
Award details come from USAspending.gov.
Description
- Abstract
- Human immunodeficiency virus (HIV) is a highly mutable virus, resulting in thousands of new infections annually. Therefore, developing effective preventive measures (i.e. vaccines) for children and adolescents remains a critical public health priority. Prior work from our group showed that a promising strategy is to elicit broadly neutralizing antibodies (BNABS) through early-life immunization, leveraging the infant immune system's unique capacity to generate these potent responses. How these responses develop with age, however, is much less understood. Current HIV vaccine strategies include bioengineered HIV ENV sosip proteins, designed to mimic the native trimerization of the HIV ENV protein and drive specific B cell lineages to produce BNABS. BG505 germline-targeting (GT)1.1 sosip trimer has demonstrated the ability to target germ-line B cell lineages and elicit strong breadth and potency in precursor CD4BS bnab responses, making IT an attractive vaccine platform candidate for protective immunity to HIV. I hypothesize that the infant B cell repertoire is distinct from that in adolescence, due to a more restricted and flexible chromatin landscape, leading to a higher frequency of HIV antigen-specific B cell responses. To test this, I propose using a translational approach using samples from the infant and juvenile rhesus macaques (RMS) immunized with the BG505 GT1.1 sosip trimer. Aim 1: determine how age at immunization influences B cell repertoire maturation and lineage evolution following germline-targeting HIV ENV immunization. I will examine this by sequencing antigen-specific B cells from the periphery in the infant and juvenile RMS. I will also use the human tonsil organoid cultural model to replicate these developmental differences in antigen-specific B cell activation. Aim 2: define age-associated epigenetic mechanisms that regulate B cell somatic hypermutation (SHM) that lead to the development of BNABS following germline-targeting HIV ENV immunization. I will test this by examining chromatin accessibility in antigen-specific B cells isolated from the periphery using atac-SEQ. Similarly, I will test whether the same distinct accessibility is observed using antigen stimulation in the human tonsil organoid model. Upon achieving these aims, I expect this work to reveal inherent, age-specific patterns in B cell mutation and evolution that shape early-life humoral immunity. These findings will define the developmental features of early-life B cells, providing a mechanistic framework to aid in the design of next-generation IV vaccines capable of inducing potent, protective bnab responses across all ages.
Quick answers
Who received award F31AI203596?
F31AI203596 was awarded to Weill Medical College Of Cornell University by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on February 14, 2027.
How much is award F31AI203596 worth?
$50,114 has been obligated on F31AI203596.
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