Reference Number: PhD Research Project 6
Location: Kilifi
Country: Kenya
Supervisor: TBC
Description:
Plasmodium falciparum antigenic diversity is a major obstacle to vaccine development and contributes to the low observed efficacy in Phase III trials of the first licensed malaria vaccine. RTS,S, which is the first licensed malaria vaccine, utilizes a single variant of the circumsporozoite protein (CSP). This vaccine demonstrated only 30% efficacy against malaria infection which may be due in part to the tremendous diversity in this antigen; we identified nearly 300 different CSP variants in a single transmission season in western Kenya. Understanding how to elicit robust immunity to parasite antigenic targets that protects against many different variants has the potential to transform the next generation of vaccine products.
Using a unique, longstanding cohort encompassing about 600 people in 75 households in a high-transmission community in Western Kenya, we can pinpoint parasite transmission events to the individual-level, characterize the variant composition of multi-strain P. falciparum exposures, and document the outcome (no infection or protected vs. infected with or without symptoms) at the variant level.
The goal of this PhD project is to leverage known exposures and clearly defined protection phenotypes within a natural system that encompasses a high degree of parasite diversity to advance multi-variant vaccine design. Specifically, the student will leverage our unique process of identifying individual infectious mosquito bites to measure antibody responses that protect against subsequent establishment of parasite infection with both homologous and heterologous strains. Antibody responses will be explored through peptide arrays populated with hundreds of naturally occurring peptide variants of specific vaccine candidate antigens. By exploring heterologous versus homologous strain-specific responses, we hope to elucidate a minimum set of antigenic variants required to confer strain-transcendent protection, facilitating the development and delivery of the next generation of P. falciparum vaccines.
The successful candidate will be awarded a full PhD fellowship through SSACAB DELTASAfrica programme and based at KWTRP, Kilifi for the PhD research.
Key qualification(s):
- Undergraduate or Masters studies in laboratory sciences (molecular biology, immunology), statistics, bioinformatics, epidemiology or a related field.
- Experience in laboratory research.
- Demonstrable experience in high-dimensional data analysis.
Other desired qualifications
- Willingness to travel to Duke University, USA for related training.
- Strong communication skills (oral and written).
- Teamwork skills.
- Demonstrable experience with programming in R (will be an added advantage).