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Effect of presentation methods on the molecular mechanism of combinatorial adjuvants

Award Number: U01AI124270
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2022

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Effect of presentation methods on the molecular mechanism of combinatorial adjuvants - PROJECT SUMMARY: Vaccination is one of the most successful public health interventions in human history. Despite the fact that many incurable and high-mortality diseases are fully controlled, and in some cases eliminated from human civilization, many other diseases remain elusive to vaccine interventions. Our ability to better understand how natural infectious pathogens trigger and control mammalian immunity by activating multiple immune-pathways and generating a combinatorial response, will greatly help the design and clinical translation of more effective vaccines against emerging infectious diseases, HIV/AIDS, cancer, etc. Most of our knowledge in stimulating vaccine adjuvants, molecules that stimulate the immune system to generate protective or therapeutic immunity against antigens, comes from pathogen/danger-associated molecular patterns (PAMPs/DAMPs) of viruses, bacteria, fungi or parasites. In natural infections, multiple adjuvants and Ag are carried inside a particle-like structure and innate immune cells experience adjuvant and antigens as a combination entity in single particles, which acts to localize and concentrate a set of synergistic stimulatory signals. Thus, we argue, that (a) in order to develop more efficacious vaccines we must understand the molecular mechanisms by which multiple adjuvants act on innate immune cells and in tandem, control adaptive immunity; and (b) the most prudent way of presenting combinations of adjuvants in vivo is through particulate carriers that mimic pathogens (Pathogen-like particles, PLPs). Variation of these carriers' properties (e.g. size, charge, composition) will affect how adjuvants interact with innate immune cells and modulate the resulting immune response; an aspect that likely occurs in natural infections as well. Our overarching hypotheses are that the combinatorial in vivo effects of two clinically-relevant adjuvants, CpG and Monophosphoryl Lipid A (MPLA), can be (a) precisely modulated by the mode of presentation (soluble, vs particulate carriers of different physical properties) and (b) better predicted by in vitro assays when delivered together as particulate carriers. To test these, we propose the following aims. Aim 1: Develop and characterize CpG/MPLA co-loaded pathogen-like-particle (PLP) adjuvants of various sizes and adjuvant- density. Aim 2: Investigate in-vitro, the molecular mechanisms involved in how various DC subsets respond to combination adjuvant formulations. Aim 3: Identify in vivo, the molecular mechanisms behind synergistic systemic immune-responses to combination adjuvant formulations. Collectively, the proposed studies will (a) greatly advance our understanding of molecular mechanisms that mediate potent priming of adaptive immunity by combination-adjuvants, (b) identify key physico-chemical parameters that control adjuvanticity of combination-adjuvants and PLPs, and (c) lead to the development of new platform technologies and reagents for combinatorial-adjuvant based human vaccines with immediate translational potential and clinical use.


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	2020	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	5	10/13/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = -$64,393 )
2023	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	001	5	9/6/2023	NON-COMPETING CONTINUATION	-$59,305
2023	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	5	5/15/2023	NON-COMPETING CONTINUATION	-$5,088
														Subtotal = -$64,393

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	002	5	6/1/2022	SUPPLEMENT FOR EXPANSION	$0
2022	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	001	5	4/1/2022	SUPPLEMENT FOR EXPANSION	$25,062
2022	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	5	11/3/2021	SUPPLEMENT FOR EXPANSION	-$25,062
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $669,597 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	001	5	5/8/2020	SUPPLEMENT FOR EXPANSION	$150,285
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	5	3/3/2020	NON-COMPETING CONTINUATION	$519,312
														Subtotal = $669,597

Issue Date FY: 2019 ( Subtotal = $523,574 )
2019	2019	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	001	4	9/4/2019	NON-COMPETING CONTINUATION	$0
2019	2019	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	4	2/28/2019	NON-COMPETING CONTINUATION	$523,574
														Subtotal = $523,574

Issue Date FY: 2018 ( Subtotal = $847,521 )
2018	2018	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	001	3	7/31/2018	NON-COMPETING CONTINUATION	$0
2018	2018	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	3	1/22/2018	NON-COMPETING CONTINUATION	$527,521
2018	2018	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	002	3	8/8/2018	NON-COMPETING CONTINUATION	$320,000
														Subtotal = $847,521

Issue Date FY: 2017 ( Subtotal = $731,175 )
2017	2017	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	000	2	2/28/2017	NON-COMPETING CONTINUATION	$531,175
2017	2017	GEORGIA TECH RESEARCH CORPORATION	505 10TH ST NW	ATLANTA	GA	30318	FULTON	USA	Allergy and Infectious Diseases Research	001	2	8/10/2017	NON-COMPETING CONTINUATION	$200,000
														Subtotal = $731,175

Issue Date FY: 2016 ( Subtotal = $548,711 )
2016	2016	GEORGIA TECH RESEARCH CORPORATION	HINMAN BUILDING	ATLANTA	GA	30332	FULTON	USA	Allergy and Infectious Diseases Research	000	1	2/19/2016	NEW	$548,711
														Subtotal = $548,711

Grand Total All Awards = $3,256,185

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Effect of presentation methods on the molecular mechanism of combinatorial adjuvants

Award Number: U01AI124270

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2022

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