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Large Scale systematic priorization of Plasmodium vivax blood stage vaccine antigens

Award Number: R01AI137154
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: 02/14/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2023

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Large Scale systematic priorization of Plasmodium vivax blood stage vaccine antigens - Summary Despite recent progress in reducing severe disease in sub-Saharan Africa, malaria remains one of the largest global public health burdens and a leading cause of mortality in children in low and middle income countries. There is an urgent need for an effective malaria vaccine because resistance has emerged to every antimalarial drug that has been publicly released to date. Vaccines against Plasmodium falciparum, the major cause of malaria in Africa, have received extensive support and are showing encouraging signs, but vaccine research for Plasmodium vivax, the major cause of malaria outside of Africa, has to date been extremely limited. This proposal will use the lessons from P. falciparum vaccine development, which for too long focussed on a limited number of candidates and did not make use of the full depth of available genomic sequence information. The central objective is to carry out the first comprehensive reverse vaccinology assessment of P. vivax blood stage antigens, combining advanced genomic and cellular techniques with ex vivo phenotyping assays. An established eukaryotic protein expression system will be used to express a library of >200 P. vivax blood stage vaccine candidates, which will be selected based on gene expression, biophysical characteristics and genomic diversity criteria. All expression constructs will be made freely available to the research community to aid global P. vivax vaccine and biology research efforts. The expressed proteins will be screened for antibody binding to confirm correct folding, and used in erythrocyte and receptor binding assays to prioritise targets for further study. Polyclonal antibodies will be raised against 100 targets and used in ex vivo P. vivax invasion phenotyping assays, to identify antibodies that block parasite invasion or growth. P. vivax parasites from both South America and Southeast Asia will be used at this stage of screening, introducing antigenic diversity at the earliest stage of target prioritization, another important lesson from P. falciparum vaccine development where strain-specific inhibitory responses derailed several promising candidates. Antibodies that provide cross- strain inhibition will be tested in combination to identify >4 highly effective and synergistic candidates for future development and potential clinical testing. The proposal will radically change the scale and pace of P. vivax vaccine development, and will produce resources of broad utility to the malaria research community.


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	2021	THE CHANCELLOR, MASTERS, AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE	UNIVERSITY OF CAMBRIDGE THE OLD SCHOOLS, TRINITY LANE	CAMBRIDGE				GBR	Allergy and Infectious Diseases Research	000	4	12/21/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = -$4,331 )
2022	2019	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX			GBR	Allergy and Infectious Diseases Research	001	2	6/29/2022	NON-COMPETING CONTINUATION	-$4,331
2022	2018	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX			GBR	Allergy and Infectious Diseases Research	000	1	6/29/2022	NEW	$0
														Subtotal = -$4,331

Issue Date FY: 2021 ( Subtotal = $318,040 )
2021	2021	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE	THE OLD SCHOOLS	CAMBRIDGE	CAMBRIDGESHIRE			GBR	Allergy and Infectious Diseases Research	000	4	2/3/2021	NON-COMPETING CONTINUATION	$318,040
														Subtotal = $318,040

Issue Date FY: 2020 ( Subtotal = $259,326 )
2020	2020	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE	THE OLD SCHOOLS	CAMBRIDGE	CAMBRIDGESHIRE	CB2 1TN		GBR	Allergy and Infectious Diseases Research	002	3	7/16/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$395,709
2020	2019	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX	CB10 1SA		GBR	Allergy and Infectious Diseases Research	000	2	5/2/2020	NON-COMPETING CONTINUATION	-$136,383
2020	2019	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX	CB10 1SA		GBR	Allergy and Infectious Diseases Research	001	2	7/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $259,326

Issue Date FY: 2019 ( Subtotal = $345,715 )
2019	2019	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX	CB10 1SA		GBR	Allergy and Infectious Diseases Research	000	2	1/25/2019	NON-COMPETING CONTINUATION	$345,715
														Subtotal = $345,715

Issue Date FY: 2018 ( Subtotal = $368,212 )
2018	2018	GENOME RESEARCH LTD	WELLCOME TRUST GENOME CAMPUS	SAFFRON WALDEN	ESSEX	CB10 1SA		GBR	Allergy and Infectious Diseases Research	000	1	2/14/2018	NEW	$368,212
														Subtotal = $368,212

Grand Total All Awards = $1,286,962

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Large Scale systematic priorization of Plasmodium vivax blood stage vaccine antigens

Award Number: R01AI137154

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: 02/14/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2023

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