Beeson Group

Malaria Immunity and Vaccines

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Overview

Every two minutes a child dies from malaria and there is an urgent need for a vaccine and new drugs to treat the disease.

Plasmodium falciparum, causes most clinical cases and deaths globally, however P.vivax also causes a high burden of disease in Asia and the Pacific region.

Our research centres on five different approaches:

  • Immunity to malaria in humans
  • Vaccines against malaria
  • New treatments for malaria
  • Mechanisms of infection of red blood cells
  • Clinical studies on malaria

Latest news:

Burnet research, published in the prestigious international journal, Immunity, reveals the discovery of a key strategy used by the body’s immune system to protect against malaria infection. The discovery shows how antibodies work in partnership with other proteins in the blood, known as complement, in blocking malaria infection, opening the door towards an effective vaccine.

“Exploiting this malaria-blocking activity is a new approach in developing a vaccine. We have shown that it is possible to effectively generate this protective immune response by immunising humans with a candidate vaccine,” Professor Beeson said.

October 2016:

New tests expand malaria vaccine horizons

September 2016:

New publication on acquired immunity to leading malaria vaccine candidates (known as PfRH5 and PfRipr): Weaver R et al, Scientific Reports 2016

We found that acquired antibodies to specific proteins expressed by P. falciparum that enable it to infect human red blood cells (known as PfRH5 and its binding partner PfRipr) are predominantly comprised of sepcific types of antibodies (known as IgG1 and IgG3). We found that the IgG3-type of antibodies were strongly linked with protection from malaria in children. These findings give new insights into the development of effective malaria vaccines, and indicate that further studies are needed to better understand how these antibodies function to block malaria, such as through interactions with complement proteins in the blood.

New publication on malaria the vaccine candidate AMA1. Drew R et al, BMC Medicine 2016

We developed a novel approach with genetically-modified P. falciparum to dissect specific immune responses. Our findings highlight the importance of AMA1 as a target of the human immune response, and how variation in this protein help malaria evade immune responses. The new findings shed light on how to develop vaccines that will effectively protect against malaria across different regions globally.

Objectives

Immunity to malaria in humans

Our aims are to identify the key targets of immunity, understand the mechanisms mediating immunity, and determine how immunity is acquired and maintained. This involves combining detailed studies of immune responses with clinical and population studies of children and pregnant women in Africa, Asia and Papua New Guinea. Studies focus on understanding how antibodies neutralize and clear malaria parasites in the blood (for both P. falciparum and P. vivax), and understanding the importance of interactions with monocytes/macrophages and other immune cells.

Vaccines against malaria

This involves identifying and prioritising candidate antigens for vaccine development, determining the optimal formulation and delivery of vaccine antigens, and developing assays to measure vaccine-induced immune responses that can be used in vaccine development and clinical trials. Studies focus on several leading candidate antigens (AMA1, EBAs, PfRh, MSP2), and also aims to identify and characterise other antigens that could be developed as vaccines. Work is also undertaken on vaccine approaches to induce potent protective immune responses.

New treatments for malaria

In response to the need for new anti-malarial drugs to combat drug resistance, identifying and developing novel compounds that inhibit replication of Plasmodium parasites is required. Having recently identified novel compounds and drugs that block the blood-stage replication of P. falciparum, and possibly other plasmodium species, on-going studies aim to develop new compounds with potent anti-malaria activity that have potential for clinical development.

Mechanisms of infection of red blood cells

During blood-stage replication of Plasmodium, the merozoite form of the parasite (the form of the malaria parasite that invades red blood cells) infects red blood cells and develops and replicates inside them. This is an essential step in the Plasmodium life-cycle that could be targeted by vaccines and novel drugs. Identifying molecular and cellular interactions involved in invasion of red blood cells by P. falciparum merozoites using novel approaches we have recently developed. We will use this knowledge to complement out research on vaccine development and drug discovery.

Clinical studies on malaria

The focus is to understand the negative consequences of malaria and how they can be prevented. This will assist with the understanding of how malaria interacts with other health problems, such as anaemia and other infections, to worsen health outcomes in children and pregnant women.

Projects