Projects

Understanding immunity mediated by the RTS,S malaria vaccine in children

We're researching the immune responses induced by the RTS,S vaccine where the burden of malaria is highest: among young children in multiple malaria-endemic countries across Africa.

Objective

The RTS,S vaccine has recently been recommended for implementation as a childhood vaccine in regions with moderate to high malaria transmission.

Although promising, the RTS,S vaccine does have important limitations. Vaccine efficacy is modest and short-lived. In children aged 5–17 months efficacy was 55% over the first 12 months after the primary course of vaccination (3 doses).

Given the rapid waning of protective immunity, a booster dose is recommended 12–18 months after completing the primary immunisation.

The precise mechanisms and correlates of immunity for RTS,S are not well understood, but this knowledge is needed to optimise the impact of the vaccine against malaria and to inform strategies to build on RTS,S to develop more protective and long-lasting vaccines.

Overall objectives

We aim to develop strategies to improve the level of protection and effectiveness of the RTS,S vaccine in malaria-endemic countries, and support the development of new more protective vaccines for the future.

Specific objectives

The project also aims to:

quantify the immune mechanisms induced by the RTS,S vaccine in children that mediate protection from malaria.
identify immune correlates of protection for the RTS,S vaccine.
understand how strain variation in malaria impacts on the effectiveness of the RTS,S vaccine.

Timeline

2019–ongoing.

Approach

We are researching the immune responses induced by the RTS,S vaccine among young children in large studies of children multiple malaria-endemic countries across Africa where the burden of malaria is highest.

We combine powerful and innovative immunological analysis that define immune functions and specific targets of immune responses with advanced biostatistical analyses and modelling approaches.

We are also analysing how polymorphisms or variations that occur in naturally-circulating malaria strains in Africa may enable the evasion of vaccine-induced immunity.

Community impact

The majority of malaria deaths and disease occurs in young children in African countries. Malaria is one of the world’s leading causes of death for young children.

By understanding how the RTS,S vaccine works to protect against malaria, and why it is not more protective, we hope to develop strategies to improve the impact of RTS,S against malaria and help advance the development of more protective and long-lasting vaccines.

This will reduce illness and death among children globally.

Student opportunities

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This project is open to students

This project is suitable for a student with an interest in vaccinology, immunology or infectious diseases.

RTS,S is the first malaria vaccine approved for wide-scale use in African infants living in areas with moderate to high malaria transmission. RTS,S, especially when used in combination with other antimalarial interventions (such as drug prophylaxis), is predicted to significantly reduce the global burden of malaria and malaria associated mortality in young infants and children.

While promising, RTS,S is an imperfect vaccine that provides only modest protective efficacy that wanes over time. Understanding the immune mechanisms that confer RTS,S-mediated protection and their response kinetics are critical to developing improved vaccines in the future.

RTS,S immunity is primarily driven by antibodies. This project will therefore investigate the fine specificity of antibodies induced by RTS,S vaccination in young African infants and children, and how this influences antibody function and the ability to protect against clinical malaria.

This will involve developing novel competition immunoassays to map antibody specificity, and leverage established assays to assess the functional abilities of antibodies to active the complement system and innate immune cells (via Fc receptors). This project links with our wider research program on understanding the RTS,S malaria vaccine (see watch a video on RTS,S).

What you'll do

The specific activities of the project can be refined based on your interests and training background as a student. These may include, but are not limited to: