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Published on: July 3, 2020
Antibodies to PfsEGXP, an Early Gametocyte-Enriched Phosphoprotein, Predict Decreased Plasmodium falciparum
Christian P Nixon1,2, Christina E Nixon1, Ian C Michelow1
1Center for International Health Research, Rhode Island Hospital and Alpert Medical School of Brown University, Providence.
Insights
Researchers identified PfsEGXP as a novel target for transmission-blocking vaccines (TBVs). Antibodies against PfsEGXP were linked to reduced Plasmodium falciparum gametocyte density in humans, supporting its potential for TBV development.
Area of Science:
- Immunology
- Parasitology
- Vaccine Development
Background:
- Immune responses targeting Plasmodium falciparum gametocytes are crucial for developing transmission-blocking vaccines (TBVs).
- Identifying specific gametocyte antigens recognized by the human immune system is key for TBV strategies.
Purpose of the Study:
- To discover novel antigens for transmission-blocking vaccines by analyzing the Plasmodium falciparum gametocyte proteome.
- To investigate the correlation between immune responses to specific antigens and gametocyte density in humans.
Main Methods:
- Utilized a whole proteome differential screening approach with plasma from a Plasmodium falciparum treatment-reinfection study in Kenya.
- Screened a complementary DNA expression library of P. falciparum gametocytes using pooled plasma from individuals with varying gametocyte carriage levels.
- Quantified gametocytemia weekly for 18 weeks in 144 enrolled males.
Main Results:
- Identified 8 parasite genes recognized by individuals resistant to gametocyte infection.
- Antibodies against one identified antigen, PfsEGXP, predicted significantly lower gametocyte density over the 18-week study period (P = .021).
- Anti-PfsEGXP responders exhibited 31% lower gametocyte density compared to non-responders (P = .04).
Conclusions:
- PfsEGXP is a novel, gametocyte-specific antigen targeted by human antibodies.
- Antibodies to PfsEGXP are associated with reduced Plasmodium falciparum gametocyte density, validating its potential as a TBV target.
- The study supports a new platform for discovering TBV antigens based on immune responses to the gametocyte proteome.
Background:
Antigametocyte-specific immune responses may regulate Plasmodium falciparum gametocyte density, providing the rationale for pursuing transmission-blocking vaccines (TBVs) that target gametocytes in the human host.
Methods:
To identify novel antigametocyte TBV antigens, we interrogated the gametocyte proteome with our whole proteome differential screening method using plasma from a treatment-reinfection study conducted in western Kenya. At the start of the high-transmission season, 144 males (12-35 years) were enrolled and treated with quinine and doxycycline, peripheral venous blood samples were obtained, volunteers were observed, and weekly blood films were obtained for 18 weeks to quantify gametocytemia. Using plasma pooled from individuals with low versus high gametocyte carriage, we differentially screened a P falciparum gametocyte stage complementary deoxyribonucleic acid expression library.
Results:
We identified 8 parasite genes uniquely recognized by gametocyte-resistant but not by gametocyte-susceptible individuals. Antibodies to one of these antigens, PfsEGXP, predicted lower gametocytemia measured over the 18-week transmission season (P = .021). When analyzed dichotomously, anti-PfsEGXP responders had 31% lower gametocyte density over 18 weeks of follow-up, compared with nonresponders (P = .04).
Conclusions:
PfsEGXP is one of the first reported gametocyte-specific target of antibodies that predict decreased gametocyte density in humans and supports our novel TBV antigen discovery platform.
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