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Engineering sustainable squalene analogues for novel vaccine adjuvant emulsions

Award Number: R01AI135673
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/16/2018
PERIOD OF PERFORMANCE END DATE: 12/31/2023

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Engineering sustainable squalene analogues for novel vaccine adjuvant emulsions - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	001	5	1/26/2024	NON-COMPETING CONTINUATION	$0
2024	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	5	11/17/2023	NON-COMPETING CONTINUATION	$0
2024	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	003	5	8/7/2024	NON-COMPETING CONTINUATION	$0
2024	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	002	5	3/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	5	10/27/2022	NON-COMPETING CONTINUATION	$0
2023	2022	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	001	5	2/2/2023	NON-COMPETING CONTINUATION	$0
2023	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	003	5	9/8/2023	NON-COMPETING CONTINUATION	$0
2023	2022	ACCESS TO ADVANCED HEALTH INSTITUTE	1616 EASTLAKE AVE E	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	002	5	6/2/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $786,095 )
2022	2022	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	002	5	1/25/2022	NON-COMPETING CONTINUATION	$786,095
2022	2022	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	003	5	9/9/2022	NON-COMPETING CONTINUATION	$0
2022	2021	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	4	1/4/2022	NON-COMPETING CONTINUATION	$0
2022	2021	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	001	4	1/6/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $786,095

Issue Date FY: 2021 ( Subtotal = $833,113 )
2021	2021	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	002	4	9/1/2021	NON-COMPETING CONTINUATION	$0
2021	2021	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	4	3/11/2021	NON-COMPETING CONTINUATION	$833,113
2021	2021	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	001	4	7/27/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $833,113

Issue Date FY: 2020 ( Subtotal = $848,166 )
2020	2020	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	3	3/19/2020	NON-COMPETING CONTINUATION	$848,166
														Subtotal = $848,166

Issue Date FY: 2019 ( Subtotal = $856,636 )
2019	2019	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	2	12/3/2018	NON-COMPETING CONTINUATION	$856,636
														Subtotal = $856,636

Issue Date FY: 2018 ( Subtotal = $806,401 )
2018	2018	INFECTIOUS DISEASE RESEARCH INSTITUTE	1616 EASTLAKE AVE E STE 400	SEATTLE	WA	98102	KING	USA	Allergy and Infectious Diseases Research	000	1	1/15/2018	NEW	$806,401
														Subtotal = $806,401

Grand Total All Awards = $4,130,411

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Engineering sustainable squalene analogues for novel vaccine adjuvant emulsions

Award Number: R01AI135673

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/16/2018

PERIOD OF PERFORMANCE END DATE: 12/31/2023

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