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Principal Investigator: Neil King
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2024
Award: $2,913,088
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY – PROJECT 5: mRNA AND mRNA-LAUNCHED NANOPARTICLE VACCINES
The goal of Project 5 is to develop generalizable approaches and platforms to design, make, and evaluate
mRNA-based vaccines for paramyxovirus, arenavirus, and phenuivirus antigens. We will leverage the industry
experience of Stuart in mRNA vaccines with the King lab’s leadership in structure-based vaccine design. We
will define strategies to optimize the designed antigens from Project 3 to further improve their performance
when delivered by mRNA. Additionally, we will combine the speed of mRNA vaccine manufacture with the
potency of nanoparticles to develop an mRNA-launched nanoparticle vaccine platform. This work will be made
possible by application of cutting-edge machine learning-based methods for protein design from the Baker lab
and deep pathogen-specific expertise in the Broder, Cross, Freiberg, Geisbert, Ikegami, and Veesler groups.
The central hypothesis underlying our approach is that mRNA vaccines will only realize their full potential when
combined with cutting-edge protein design. Specifically, proteins designed for optimal secretion and localization
within the membrane can improve immunogenicity. Additionally, using mRNA vaccines to launch genetically
encoded protein nanoparticle immunogens from cells in vivo can enhance the potency and durability of the
response. In summary, we will leverage the computational tools and methods developed in Project 1, along
with the antigen and nanoparticle design work from Projects 3 and 4, to develop new, generalizable strategies
for mRNA vaccine design for arenaviruses, phenuiviruses, and paramyxoviruses. In Years 4-5, we will explicitly
test if these strategies can be generalized to other members of these viral families in a “live-fire exercise”
intended to mimic an outbreak situation.
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