Tuesday, October 21, 2025 10/21/2025

Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplification

Award Number: R01AI173171
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: 07/01/2025
PERIOD OF PERFORMANCE END DATE: 06/30/2028

Group Awards By:

View Award Description

Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplification - Elimination of Plasmodium vivax (Pv) malaria parasites would greatly benefit from a blood-stage vaccine. PvDBP is a parasite ligand involved in erythrocyte invasion through the interaction with its human receptor, the Duffy protein. This interaction is critical for the parasite’s entry making PvDBP the most advanced candidate for a blood-stage vaccine with Phase II clinical trials undergoing. Recent work has identified and characterized human monoclonal antibodies (humabs) that allow strain-transcending neutralization of parasites regardless of their PvDBP sequence diversity. However, we have demonstrated that Pv collected in Cambodia with multiple copies of the PvDBP gene were able to overcome in vitro neutralization by these humabs. These observations provided the first evidence for an evolutionary advantage for pvdbp amplification, widespread in Pv populations, and created a new paradigm in which to consider pathogen immune evasion mechanisms. These results raise the concern that implementation of a PvDBP vaccine may select for multi-pvdbp copy parasites. The overall goal of this proposal is precisely to determine if pvdbp amplification will likely compromise a PvDBP vaccine strategy. The first Specific Aim (SA) is to determine to what extent multi-pvdbp copy parasites genetically distant from Cambodian isolates respond to anti-PvDBP humabs and to evaluate if pvdbp amplification is associated to Duffy polymorphisms in human populations. By evaluating the in vitro neutralization by anti-PvDBP humabs of single and multi-pvdbp copy parasites from Ethiopia, we will be able to evaluate the extent of the immune evasion phenotype conferred by pvdbp amplification described with Cambodian Pv. By (i) associating in vitro invasion rates with the full-length Duffy sequences of invaded erythrocytes, and (ii) prospectively testing for association between pvdbp copy number and human Duffy sequences in participants enrolled in longitudinal cohorts in Cambodia and in Ethiopia, we will be able to determine the relation between pvdbp amplification and Duffy human polymorphism. Our second SA will be to evaluate the within-hosts and within-population dynamics of pvdbp amplification over time. Through the analysis of the serological dynamics of our longitudinal cohorts’ participants, the measure of Pv infections and the pvdbp copy number of infecting parasites, we will be able to test if the gene amplification is selected in vivo by the immune status of human hosts and how it correlates with changes in Pv prevalence in the population. In vitro experimental evolution of Pk lines will provide complementary evidence for selection of pvdbp amplification by anti-PvDBP humabs. Our third SA will be to decipher the molecular mechanisms enabling multi-copy parasites to evade anti-PvDBP humabs’ neutralization. We will specifically test if immune evasion results from increased protein quantity produced by multi-copy parasites and/or from epitope variations through multiple, different alleles and variants present simultaneously in a given parasite. Through a combination of phenotyping and genomic approaches, our results will provide invaluable data to inform on strategies to overcome this immune evasion in the context of vaccine development. .


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 = $601,913 )
2025	2025	INSTITUT PASTEUR DU CAMBODGE	5 BOULEVARD MONIVONG	PHNOM PENH				KHM	Allergy and Infectious Diseases Research	000	3	9/10/2025	NON-COMPETING CONTINUATION	$538,388
2025	2025	INSTITUT PASTEUR DU CAMBODGE	5 BOULEVARD MONIVONG	PHNOM PENH				KHM	Allergy and Infectious Diseases Research	001	3	9/12/2025	SUPPLEMENT FOR EXPANSION	$63,525
														Subtotal = $601,913

Issue Date FY: 2024 ( Subtotal = $549,692 )
2024	2024	INSTITUT PASTEUR DU CAMBODGE	5 BOULEVARD MONIVONG	PHNOM PENH				KHM	Allergy and Infectious Diseases Research	000	2	6/18/2024	NON-COMPETING CONTINUATION	$549,692
														Subtotal = $549,692

Issue Date FY: 2023 ( Subtotal = $626,201 )
2023	2023	INSTITUT PASTEUR DU CAMBODGE	5 BOULEVARD MONIVONG	PHNOM PENH				KHM	Allergy and Infectious Diseases Research	000	1	7/17/2023	NEW	$626,201
														Subtotal = $626,201

Grand Total All Awards = $1,777,806

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Extent, dynamics and mechanisms of Plasmodium vivax immune evasion caused by PvDBP gene amplification

Award Number: R01AI173171

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: 07/01/2025

PERIOD OF PERFORMANCE END DATE: 06/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer