# Engineering sustainable squalene analogues for novel vaccine adjuvant emulsions

> **NIH NIH R01** · ACCESS TO ADVANCED HEALTH INSTITUTE · 2022 · $786,095

## Abstract

Project Summary
Global pandemic influenza vaccine production capacity is insufficient to meet the expected demand in the event
of a highly lethal influenza pandemic. Current H5N1 vaccines require high antigen doses (e.g. 90 μg) or are
combined with squalene-based oil-in-water emulsion adjuvants for enhanced and broadened immunogenicity
as well as antigen dose sparing. Squalene is a naturally occurring oligoisoprene (i.e. a very low molecular weight
polymer of isoprene) derived from shark liver, a source with sustainability concerns. Moreover, the biological
mechanisms of action of squalene are still not well understood and no systematic comparison of the adjuvant
activity of squalene emulsions compared to emulsions based on analog oligoisoprenes has been reported in the
literature. This proposal defines a program to develop the sustainable production of various oligoisoprene
analogues of squalene using bioengineered organisms and synthetic polymer chemistry. Selected structures will
then be formulated in oil-in-water emulsions and evaluated for physicochemical stability. Importantly, we
propose to identify structure-activity relationships (SAR) by employing squalene and oligoisoprene analogues in
in vitro human and in vivo mouse models in combination with an H5N1 influenza antigen. Moreover, the ability
to further enhance adjuvant activity by chemical modification to improve physicochemical properties of selected
oligoisoprene structures will be evaluated. The technology generated could be applicable to many other vaccines
that have need of emulsion-based adjuvants for antigen dose sparing or enhanced immune responses.

## Key facts

- **NIH application ID:** 10370340
- **Project number:** 5R01AI135673-05
- **Recipient organization:** ACCESS TO ADVANCED HEALTH INSTITUTE
- **Principal Investigator:** Christopher B Fox
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $786,095
- **Award type:** 5
- **Project period:** 2018-01-16 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370340

## Citation

> US National Institutes of Health, RePORTER application 10370340, Engineering sustainable squalene analogues for novel vaccine adjuvant emulsions (5R01AI135673-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10370340. Licensed CC0.

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