Characterisation of bnAb precursors and vaccine-induced antibody responses to germline-targeting immunogens to inform HIV vaccine design

Reference Number: PhD Project 6/2024

Location: Kilifi

Country: Kenya

Supervisors: Dr Eunice Nduati,

Coupervisors: Dr Daniel Muema and Dr Michelle Muthui

 

OVERVIEW

This study seeks to explore the diversity of the antibody repertoire in African populations, which so far has yet to be extensively characterised. The analysis can highlight novel alleles not included in the current reference databases and hence enable the generation of more inclusive reference databases. Additionally, the repertoire characterisation will enable the assessment of frequencies of precursors for the various bnAb classes relevant to HIV vaccine design within the African population, which could serve as a guide to designing regionally effective vaccines.

Aside from characterising BCR sequences, the project will seek to evaluate the induction of functional responses post-vaccination with HIV GT immunogens or HIV trimers using samples from a recently completed clinical trial, the G003 trial. Furthermore, this work will seek to evaluate the utility of vaccinating PLWH as a strategy for maturing previously existing responses to generate functional responses that can suppress viraemia. Our study will offer insights into the appropriateness of this strategy and potentially inform the design of efficacious immunogens for use in both HIV naïve and PLWH.

The student’s work will focus on characterising the antibody repertoire at baseline using existing data as well as samples from PLWH who were vaccinated with HIV envelope trimers. After this, the student will spend another year assessing the properties of GT-specific B cell repertoires from the first objective with regard to their binding affinities to HIV immunogens and neutralisation phenotypes. After this, the student will spend about half a year evaluating the impact of B cell repertoire properties (binding and neutralisation phenotypes) on vaccination responsiveness by carrying out various statistical analyses of the data collected. They will then spend the remaining period of the fellowship writing up their thesis.

The successful candidate will be awarded a full PhD fellowship through the Sub-Saharan African Network for Tuberculosis (TB) and HIV Research Excellence (SANTHE) Programme based at KWTRP, Kilifi, for the PhD research.

 

SCOPE OF SUPPORT

This is a four-year PhD studentship to be based at KWTRP. Dr. Eunice Nduati, Dr. Daniel Muema and Dr. Michelle Muthui will supervise the candidate. SANTHE will provide the selected candidate with a monthly stipend, medical insurance, and financial support to cover tuition, academic-related fees, travel expenses, and research expenses. 

 

SELECTION PROCESS

Shortlisted candidates will be invited for an interview either in person or by videoconferencing. The successful candidate in the interview will be offered PhD training support.

The PhD studentship will commence in October 2024.

The closing date for completed applications is August 10, 2024.

Click here to apply