Paolo Rossi Castelli 8 September 2022 19 min read

A new monoclonal antibody to fight malaria

A new monoclonal antibody to prevent malaria has been developed in the USA at the institute led by Anthony Fauci. It blocks a protein needed by plasmodium (the infectious element transmitted by anopheles mosquitoes) to enter skin cells.

The fight against malaria appears to be close to major breakthroughs. A study coordinated in the United States by the National Institute of Allergy and Infectious Diseases (the institute headed by Anthony Fauci) suggests that the most effective strategy for curbing this challenging disease is through a new monoclonal antibody, which could complement vaccines.

The results of the research have been published in the New England Journal of Medicine, one of the world’s most important medical publications.

Malaria is a disease carried by mosquitoes of the genus anopheles, which transmit the infectious agent, a micro-organism called plasmodium, and is prevalent in tropical and subtropical countries. Plasmodium’s life cycle is extremely complex and involves numerous phases, with crucial steps in both humans and mosquitoes, and with asexual and sexual reproduction.

This has always made it extremely difficult to break the chain of events that occur after a bite (there is almost always plasmodium, at various stages of the cycle, that manages to survive, develop resistance and reproduce). This explains why drugs have produced unsatisfactory results up to now, and why as many as 240 million people worldwide were infected last year, with hundreds of thousands of deaths.

A successful strategy against malaria

To find a solution, US infectiologists have tried a different approach, studying antibodies in the blood of a volunteer who had received an experimental malaria vaccine, and had responded particularly well to the disease.
Among the many antibodies found in the blood, the researchers selected one, called L9, which seemed promising, as it is directed against one of the proteins (CSP-1) which is essential for plasmodium to pass through the skin. From there, the micro-organism is carried by the blood to the liver, where it is much more difficult to stop. According to researchers the L9 antibody could be a winning strategy to stop plasmodium spreading.

Another antibody against malaria, called CIS43LS was developed and tested on a small number of patients at the National Institute of Allergy and Infectious Diseases last year. However L9 appeared two to three times more powerful and was also easier to administer (subcutaneously) while CIS43LS must always be injected into a vein. This is why researchers decided to 'target' L9, enhancing it in the laboratory with genetic engineering techniques and then making it multiply in large numbers (this is a monoclonal antibody). The 'reinforced' version of L9, called 'L9LS', was administered in various dosages to 17 volunteers.

Once the procedure had been proved harmless, between two and six weeks after treatment the trial participants, together with untreated people, were bitten five times on the arm in the laboratory by anopheles mosquitoes, and then infected, according to a protocol used for decades at the National Institute of Allergy and Infectious Diseases. This protocol allows early intervention if a drug or vaccine does not work, to preventing the infection from spreading (all the participants in this study were of course volunteers).

Very high protection against malaria

The result was that the monoclonal antibody protected 15 out of 17 people and was 88% effective, while all members of the control group (i.e. all the untreated volunteers) were infected by the mosquitoes (and immediately cured, without further complications and without actually developing the disease).

The antibody was also effective in four of the five participants who had received the lowest dose. According to calculations, protection would last for a minimum of six months to a year and this, according to Fauci, could be a major big step forward, for example in treating children, who are still some of the main victims of the disease (children under five account for 80% of deaths from malaria).

The trial is now continuing, including on children from 5 months to 10 years of age, in Mali and Kenya, countries where malaria is endemic and where the trial aims to verify the effectiveness of one or two doses of antibody over a period of 6-12 months. If the results confirm the data of phase 1 (the tests on 17 patients) - Fauci commented - there could be a significant reduction in infections and, above all, in infant mortality, paving the way for a new therapeutic approach that is potentially much more effective, and easily implemented without a great deal of organisational effort, unlike those studied so far.

 

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.