Novel TLR-4 Agonists as Vaccine Adjuvants

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: ALAN THOMAS JOHNSON
Organization: HAWAII BIOTECH, INC.
Fiscal Year: 2024
Award: $204,860
Funding agency: National Institute of Allergy and Infectious Diseases

Abstract/Project Summary
 Along with the many benefits of a global economy hides the ever-present risk for the world wide spread
of infectious disease. While significant outbreaks of the flu in the recent past involving millions of individuals
could be contained, the emergence and rapid spread of the SARS-CoV-2 virus revealed how vulnerable and
unprepared the world population was to combat a previously unknown human pathogen.
 To limit the loss of life and economic disruption resulting from a future global event, steps toward
pandemic preparedness are needed. A major component of being prepared is having the necessary tools
available to act quickly to protect human health. In the ongoing pandemic, vaccines emerged as the best way
to protect healthy populations and prevent hospitalization or death among those individuals who become
infected. However, vaccine availability and logistical constraints regarding their distribution has left a significant
proportion of the world’s population still waiting for their first dose. The ability to quickly discover and develop
vaccines which can be administered on a large scale is one solution towards solving this current problem.
 In support of this effort, it is the goal of this Phase I project to identify TLR4 agonists with
immunostimulatory activity suitable for the development of safe and effective vaccine adjuvants. To achieve
this goal, we will combine our years of expertise in medicinal chemistry and vaccine research and development
toward completing the following specific aims: 1) Establish efficient synthesis routes for pure tri-acylated
monophosphate derivatives of sucrose; 2) Identify TLR4 agonists using cell-based assays, determine their
cytokine production profiles, and compare them to the full TLR4 agonist mono-phospholipid A (MPLA); and 3)
Determine the immunogenic potency and safety profiles of selected sucrose based TLR4 agonists in mice and
compare them against an existing subunit protein vaccines targeting West Nile Virus. We expect the product
from this research to enable the development of novel adjuvants to support the preparation of new vaccines to
combat current and future disease threats.

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