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Targeting Conserved Molecular and Structural Features of Apicomplexans Towards a Rational Vaccine Design

Award Number: R21AI176186
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: 12/12/2023
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Targeting Conserved Molecular and Structural Features of Apicomplexans Towards a Rational Vaccine Design - PROJECT SUMMARY_____________________________________________________________________ Parasitic diseases remain a problem worldwide largely due to the lack of vaccines to effectively interrupt transmission or infection, as parasites often develop resistance to drugs. A combination of different factors principally drives the lack of vaccines against parasitic diseases, including a limited understanding of the nature of the humoral immune response and difficulties in proper expression of the candidate immunogen. Our current work suggests that the GPI anchor has a vital role in humoral immune response to GPI-anchored proteins (GPI- APs) and most vaccine efforts have utilized GPI-APs - which constitute the bulk of surface proteins in parasites, as immunogens. However, in these vaccine formulations, the GPI-APs are without the GPI anchor to enable soluble expression of such proteins. In this grant submission, we have shown that de-lipidation of the GPI anchor significantly reduces antibody reactivity to GPI-APs of Toxoplasma gondii, a widespread Apicomplexa parasite of animals. We hypothesize a role of the GPI anchor in humoral immune response and propose using mRNA technology as an efficient method for accurate delivery of GPI-APs to the immune system to understand its role following vaccination. We also propose the use of mRNA vaccines for the efficient delivery of highly conserved antigens of the parasite's invasion machinery, a handful of which we propose as excellent targets to halt invasion of apicomplexans. Thus, we will employ tools in immunology, molecular parasitology, vaccinology, and biochemistry to dissect the aims of the study. In Aim 1, the role of the GPI anchor in humoral immunity to T. gondii will be deciphered by comparing vaccine efficacies of parasite GPI-APs with and without their GPI anchorage following immunization. In Aim 2, the invasion machinery of T. gondii will be targeted by vaccine- elicited antibodies against conserved apical proteins of the plasma membrane that confer fitness to the parasite. With the overall goal of the project being to block infection of T. gondii and apicomplexans in general, this R21 proposal will provide new insights in vaccine development against parasitic diseases.


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: 2025 ( Subtotal = $237,569 )
2025	2025	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	000	2	11/8/2024	NON-COMPETING CONTINUATION	$237,569
2025	2025	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	001	2	8/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $237,569

Issue Date FY: 2024 ( Subtotal = $219,554 )
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$21,955
2024	2024	UNIVERSITY OF CALIFORNIA, MERCED	5200 N LAKE RD	MERCED	CA	95343	MERCED	USA	Allergy and Infectious Diseases Research	000	1	12/12/2023	NEW	$197,599
														Subtotal = $219,554

Grand Total All Awards = $457,123

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Targeting Conserved Molecular and Structural Features of Apicomplexans Towards a Rational Vaccine Design

Award Number: R21AI176186

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: 12/12/2023

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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