In a discussion with Malaria No More, Dr. Joshua Tan talks about a new study at the National Institutes of Health (NIH) that identified a novel class of antibodies that binds to a previously untargeted portion of the malaria parasite that could lead to new prevention methods.
You and your team recently announced the discovery of a novel class of anti-malaria antibodies. Can you tell us about it?
TAN: Antibodies are simply special proteins made by your immune system. One of their primary goals is to fight harmful invaders, like viruses, bacteria, or parasites. When it comes to malaria, the disease is caused by a parasite called Plasmodium, which enters the body through the bite of an infected mosquito.
Anti-malaria antibodies specifically target the Plasmodium parasite. They’re a bit like missiles in the body that stop the pathogen from carrying out its function or they end up destroying the pathogen. They work by recognizing certain parts of the parasite, like its proteins, and stopping it from infecting your liver cells or red blood cells, which are essential for the parasite to grow and cause the disease.
Vaccines can help your body produce these antibodies ahead of time, so if you’re exposed to the malaria parasite, your immune system is ready to attack it quickly. At the NIH, we’re also studying how to directly give people these antibodies, almost like a protective shield.
The circumsporozoite protein (CSP) is the main protein found on the surface of the sporozoite stage of the malaria parasite, and it has been a primary target for malaria vaccines and monoclonal antibodies. Initially, we were trying to find an antibody response against non-CSP antigens. By exploring non-CSP antigens, our hope was to develop additional tools for malaria prevention and treatment - and complement the existing interventions.
Through our research, we instead found new antibodies that target a hidden site within CSP that is not present in the malaria vaccines. We still have to test it more formally, but it is very likely that these antibodies won’t interfere with the existing malaria vaccines. So that’s useful and very exciting.
How significant of a gamechanger is this discovery?
TAN: More work is still needed, so it’s a big question. But we’re hoping this will work well together with the existing malaria vaccines. The first malaria vaccine introduced, RTS,S, was found to have a 36% efficacy rate in reducing malaria cases after 4 doses children aged 5-17 months over four years. But its potency decreases over time, and additional booster doses are needed to sustain immunity. The second malaria vaccine, R21, has an efficacy of about 75% in reducing malaria cases over a year in children under 3 during a phase 3 trial. But it also requires multiple doses to maintain efficacy, since immunity can wane over time.
We expect that one potential application of this antibody will be for those who will later get the malaria vaccine in Africa, particularly infants. But if we can find an antibody with five to ten-fold higher potency than those currently available, this could be a real game-changer in making antibodies much more affordable and broadly used.
Are more malaria tools still needed?
TAN: In clinical trials, antibodies have proven to be quite safe and effective in preventing malaria, even in endemic regions. So, these are tools that have gained a lot of interest. But a big issue is still the cost.
So, I think the consensus in the field is that we still need more tools if we are going to eliminate malaria. As a researcher, we need to keep looking at everything, like more drugs and antibodies are still extremely valuable. But we really can’t rule out anything at the moment in terms of what can help us build stronger protections against malaria.
As a malaria researcher, do you see malaria elimination on the horizon?
TAN: I’m hopeful! But at this point, it depends on what we find in the next few years or the next decade, because we still need better tools, such as next-generation antibodies, vaccines or drugs. If we can significantly improve vaccine efficacy and we have vaccines or antibodies that can last for a long time, then I would say malaria elimination could be a target.
What are you working on next?
TAN: At the NIH, we will continue to try to find new antibodies and modify antibodies we have identified to alter their DNA sequence to increase their potency against the parasite. Our hope is that we can also design vaccines against the new target site that we identified.
Malaria is a global issue and important for everyone, even for people living in the United States. Here in the United States, a few cases of malaria have cropped up over the last few years. Plus, people are traveling more and that includes to regions with malaria.
If, for example, we can get to a point where we can provide rapid protections that last for months, as opposed to tablets or drops that are taken daily, that could be very useful for many of us.
Anti-malaria antibodies are an exciting way to prevent the disease and save lives, but they are not the only way. But with more innovative tools and technologies, ending malaria will hopefully be achievable.
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