Defining protective antibody responses induced by the novel RH5.2-VLP malaria vaccine

Overview

The world urgently needs an effective malaria vaccine. Malaria is a devastating disease, infecting 247 million people and causing 619,000 deaths in 2021 alone. Alongside making people sick, it stops them working and going to school, keeping people trapped in poverty.

Despite major efforts to prevent, diagnose, and treat malaria, numbers are rising due to challenges such as increasing drug and insecticide resistance. An effective vaccine will help overcome these challenges, improving and saving countless lives.

My project will investigate how the body reacts to a new malaria vaccine ("RH5.2-VLP"). It will answer three vital questions: Does this new, innovative vaccine provide better immunity than older vaccines? Can targeting new parts of the immune system slow malaria growth? Do different malaria strains respond to our new vaccine differently?

These answers will play a pivotal role in developing our new vaccine further, preparing it for real-world use. Going Deeper

Existing vaccines target malaria parasites as they enter the body but offer limited protection. However, I will investigate what happens if we target the parasite during its later "blood-stage", when it invades red blood cells and triggers illness. This different approach holds great potential, working alone or even alongside existing vaccines for greater impact.

Recently, for the first time, a "blood-stage" vaccine showed that it can slow parasite growth. This vaccine ("RH5.1") is based on a parasite protein ("RH5") needed to invade red blood cells. Our new vaccine takes the parts of RH5.1 that cause the strongest reaction and then uses new technology to build tiny "virus-like" vaccine structures.

I am leading the first human trial of "RH5.2-VLP", vaccinating volunteers in Oxford. This means I am uniquely placed to complete further vital research into how the body reacts to this vaccine. I will:

Compare the human immune response to "RH5.2-VLP" with that to "RH5.1". I will examine a substance in the blood ("IgG antibodies") made by the body in response to vaccination. I will measure how many antibodies are made, and where and how well they stick to the vaccine.

I will also assess how well they slow parasite growth in the lab. This will help us understand how these antibodies work and how the body reacts to different vaccine types. These findings will guide further testing in African trials.

Investigate other immune responses that we can target. Previous studies suggest that levels of another antibody in the blood ("IgA") and parasite growth might be connected. I will test if IgA can stop parasites growing and, if so, investigate how that happens. This may lead to new vaccines targeting these antibodies.

Study different malaria strains. The same antibodies against RH5 affect different malaria strains by different amounts. We don't know why this is. I will investigate if it is linked to differences in RH5 genes or the amount of RH5 on the parasite. Studying new parasites from Senegal, along with well-studied lab strains, should help predict the vaccine's real-life effectiveness.

These findings will guide how we field-test this vaccine in Africa and help us to make an even better vaccine. They will inform both malaria research and broader vaccine development. Ultimately, they have the potential to save and improve lives for the millions affected by malaria, particularly the vulnerable - young children and expectant mothers - who bear its brunt.