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Targeted Nanoparticle Vaccine Approach for Protection Against Encapsulated Pathogens

Award Number: R21AI113517
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: 04/15/2015
PERIOD OF PERFORMANCE END DATE: 03/31/2017

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Targeted Nanoparticle Vaccine Approach for Protection Against Encapsulated Pathogens - ¿ DESCRIPTION (provided by applicant): Most successful human vaccines elicit protective antibodies. CD4+ T cell help is essential for a strong antibody response, especially against poorly immunogenic polysaccharide antigens. To accomplish this, polysaccharide antigens are typically conjugated to highly immunogenic T cell epitopes. Unfortunately, this approach is expensive, only targets a subset of capsular polysaccharide antigens, and depends on allelically variable CD4+ T cell help. We and others have recently identified a new source for help for B cells which can be harnessed to overcome these limitations, the invariant Natural Killer T (iNKT) cells. iNKT cells are an innate glycolipid-specific lymphocyte subset of T cells restricted to the non-polymorphic antigen presenting molecule CD1d which rapidly produce cytokines when activated. Because CD1d is non-polymorphic, or the same in all people, iNKT cells should respond to glycolipids equally well in everyone. Furthermore, glycolipids are overwhelmingly safe for humans and can serve as robust adjuvants for co-administered protein and polysaccharide antigens, especially when incorporated in nanoparticles. Nanoparticle vaccines can be made of safe, well-studied, biodegradable polymers, enhance the activity of encapsulated glycolipid adjuvants 1000 fold, and can be embedded with B cell antigens to facilitate their targeting and uptake by a relevant B cell subpopulation. The overall objective of this proposal is to use nanoparticle delivery of glycolipid adjuvant plus polysaccharide B cell antigen to protect mice against systemic infection with an encapsulated pathogen. In Aim 1 we will vaccinate mice with glycolipid plus polysaccharide embedded nanoparticles to assess which route of administration induces high titer class-switched antibodies, and protects best against two different in vivo murine models of Streptococcus pneumoniae infection. In Aim 2 we will use mice to compare how well soluble vs nanoparticle-embedded glycolipids enhance protective antibody responses induced by current human S. pneumoniae polysaccharide-based vaccines. We will also culture human peripheral blood cells to test which form of glycolipid adjuvant best enhances human polysaccharide-specific B cell responses. If successful, this line of research will drive the development of a widely applicable iNKT cell-targeted vaccine strategy which, given the non-polymorphic nature of CD1d, may be universally effective in all people. In turn, this vaccine can protect and improve human health, reduce the burdens of illness, and enhance the nation's economic well-being.


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: 2017 ( Subtotal = -$30,869 )
2017	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	002	3	8/8/2017	NON-COMPETING CONTINUATION	-$30,869
2017	2015	TRUDEAU INSTITUTE, INC.	154 ALGONQUIN AVE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	4/10/2017	NEW	-$30,028
2017	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	001	2	4/10/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$30,028
														Subtotal = -$30,869

Issue Date FY: 2016 ( Subtotal = $136,470 )
2016	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	002	3	3/16/2016	NON-COMPETING CONTINUATION	$190,625
2016	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Allergy and Infectious Diseases Research	001	2	1/26/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$183,745
2016	2015	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	1/26/2016	NEW	-$237,900
														Subtotal = $136,470

Issue Date FY: 2015 ( Subtotal = $292,500 )
2015	2015	TRUDEAU INSTITUTE	ALGONQUIN AVENUE	SARANAC LAKE	NY	12983	FRANKLIN	USA	Allergy and Infectious Diseases Research	000	1	4/8/2015	NEW	$292,500
														Subtotal = $292,500

Grand Total All Awards = $398,101

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Targeted Nanoparticle Vaccine Approach for Protection Against Encapsulated Pathogens

Award Number: R21AI113517

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: 04/15/2015

PERIOD OF PERFORMANCE END DATE: 03/31/2017

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