# Core E: Phylogenetic and mutational scanning

> **NIH NIH U19** · UNIVERSITY OF WASHINGTON · 2024 · $2,568,140

## Abstract

PROJECT SUMMARY – CORE E: PHYLOGENETIC AND MUTATIONAL SCANNING
This Core will use cutting-edge experimental and computational techniques to ensure that the vaccines target
the full relevant evolutionary breadth of the prototype virus families, and to map the breadth and specificity of
vaccine-elicited antibody responses. To do this, the Core will combine sequencing and phylogenetic analyses
with deep mutational scanning to characterize viral diversity and its impact on the vaccines. First, existing
sequence data on each of the prototype viruses will be integrated into the nextstrain platform to facilitate easy
surveillance and phylogenetic analyses. These data will then be used to inform the creation of phylogenetic
and deep mutational scanning libraries to experimentally characterize the natural and possible future
mutational diversity of the key viral glycoproteins. The libraries will utilize a powerful new pseudotyped lentiviral
deep mutational scanning system that enables variants of any viral entry glycoprotein to be characterized at
high-throughput using safe non-replicative virions at biosafety level 2. For each prototype viral entry
glycoprotein, the Core will create two types of libraries: phylogenetic libraries that contain variants spanning the
natural diversity of that virus, and deep mutational scanning libraries that contain all amino-acid mutants of key
representatives of each virus. These pseudotyped lentiviral libraries will be used to characterize how all natural
and mutational variants of the viral glycoproteins mediate entry in cell culture, and are recognized by
monoclonal and polyclonal serum antibodies. Initially, the resulting information will inform the design and
testing of the immunogens in the Center Projects. Then as these immunogens proceed into testing, the
libraries will be used to map the specificity and breadth of the elicited neutralizing responses. Taken together,
this Core will therefore provide a resource that can inform the Center Projects through all steps from initial
immunogen design to characterization of vaccine-elicited responses.

## Key facts

- **NIH application ID:** 10861410
- **Project number:** 1U19AI181881-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jesse D Bloom
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,568,140
- **Award type:** 1
- **Project period:** 2024-08-12 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861410

## Citation

> US National Institutes of Health, RePORTER application 10861410, Core E: Phylogenetic and mutational scanning (1U19AI181881-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10861410. Licensed CC0.

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