By Vivian Ihechu
As Nigeria and other African countries continue to seek ways to prevent malaria, monoclonal antibodies (mAbs) are offering a strong hope.
Dr Kayla Andrews, the Scientific Programme Leader at Bill and Melinda Gates Medical Research Institute (MRI), is giving this assurance.
Andrews spoke about the Institute’s efforts in the clinical development of its monoclonal antibody (mAbs) – the Gates MRI RSM01 – MAM01.
According to Andrews, RSM01 is the institute’s prophylactic antibody candidate for prevention of malaria tranmitted by plasmodium falciparum.
“mAbs represents one of the most important medical innovations in modern pharmacology,’’ she says.
Prophylactic means a medicine or course of action used to prevent a disease.
Andrews says due to the limitations of existing control strategies, coupled with the impact malaria has on children in low and middle-income countries, Gates MRI initiated the development of the monoclonal antibody (mAb).
The scientist says the study is currently in clinical development.
According to Gates MRI Fact Sheet, Malaria is a mosquito-borne illness that has afflicted people around the world for thousands of years.
It is a preventable and treatable disease; yet, in 2022 ,there were an estimated 249 million new malaria cases worldwide and approximately 608,000 deaths in 85 countries.
Sub-Saharan Africa accounted for 94 per cent of malaria cases and 95 per cent of malaria deaths in 2022.
Children under the age of five years accounted for 80 per cent of all malaria deaths in the region.
For two years, the COVID-19 pandemic affected the fight against malaria, disrupting prevention and treatment services and leading to additional 63,000 malaria deaths and additional 13 million cases.
Andrews notes that malaria can be prevented by avoiding mosquito bites, taking preventive medicines, sleeping under long-lasting insecticide-treated bed nets, and through vector-control interventions, among other means.
“New malaria vaccines have shown to significantly reduce malaria, especially the more severe and deadly, among children.
“However, new and better tools are desperately needed,” she says.
Recently, the World Health Organization recommended that children from five months of age in regions with moderate-to-high plasmodiumfalciparum malaria transmission should be given the RTS,S/AS01 (MosquirixTM) vaccine to reduce malaria disease burden.
Analysts are, however, worried that modest efficacy and restricted supply may limit the impact.
While praising successes in efforts at preventing malaria, Andrews believes that a huge sense of urgency is still needed to generate new tools in the fight against malaria.
According to her, Gates MRI is developing the prophylactic mAb in partnership with Atreca, a biotechnology company.
She is convinced that the mAb can provide lengthened protection against malaria caused by plasmodium falciparum.
She is hopeful that the monoclonal antibody will complement other established preventive strategies.
“It has been exciting; first, with the rollout of the very first world malaria vaccine, RTS,S/AS01, then the new R21 vaccine.
“We also have, of course, our insecticide-treated nets, the scale of seasonal prevention for children that are at high risk of severe malaria.
“With the effective tools that we have in our arsenal, the monoclonal antibody is a complementary tool in the fight against malaria.’’
Giving an insight into monoclonal antibodies, she explains that human bodies naturally produce antibodies to fight infections.
According to her, this happens anytime a human being gets infected with any pathogen, whether COVID or RSV, Ebola or flu.
According to Andrews, for the diseases that immune systems have difficulty overcoming as with COVID-19 researchers are developing mAbs which, when injected, will eliminate the infection and remain in the body for months to tackle re-infections.
“Monoclonal antibodies usually have fewer off-target effects than small-molecule drugs in most patients. They can be produced on a large scale in bioreactors.
“Monoclonal antibodies are, in most cases, derived from individuals that have developed antibodies to fight against the infection.
“What we tried to do is to select a trial of these antibodies and select the potent antibody – the one that elicits the strongest protections – and we select these really potent antibodies for further optimisation, for development to make them into a product.
“Another way of thinking about it is: a monoclonal antibody is something that is naturally produced, and we will use, try and take the best one that we can find and make it even stronger.
“There is a lot that goes into that, in terms of making sure that it has the efficacy that we want and the duration of protection that we want,’’ she explains.
Andrews says there are three monoclonal antibodies currently in clinical development for the prevention of plasmodium falciparum malaria infection.
“Two of them are the NIH antibodies, CIS43LS, and the third is our antibody at the Gates MRI, the RSM01.
“Each of these three antibodies targets slightly different epitopes, and they have slightly different targets on where they bind the malaria parasite.
“The M01 MRI antibody is being worked on in partnership with Atreca, and it has been licensed,” she adds.
The scientist discloses that the Gates MRI is currently evaluating the safety, efficacy and pharmacokinetics of MAM01 in a phase 1 first-in-human clinical trial in adults.
“Once the safety, tolerability, pharmacokinetics and efficacy of MAM01 are established in adults, the goal will be to conduct clinical studies in the most vulnerable population (children older than three months and younger than five years old) to assess the safety and ability of MAM01 to prevent P. falciparum infection.
“We finished the development of this antibody and filed our IND, our investigation of new drug application.
“We are in phase one study now. It is ongoing at the University of Maryland, to show the safety of the antibody in certain doses.
`’The reason for this is that we want to make sure that our antibody is safe and that it is providing protection,” Andrews says.
She emphasises that all tools to fight malaria are complementary.
Addressing the uniqueness of monoclonal antibodi, she says: “ What is unique as compared to a vaccine is that, generally speaking, vaccines require your body to mount an immune response.
“This takes time. This also requires multiple doses of the vaccine.
“For a monoclonal antibody, the idea is that this will be a single touch point with the healthcare system, a single shot that can provide near immediate protection – near immediate because, if it is IV, it is protection that day, but if it is administered intramuscularly or subcutaneously, then, the time to the maximum concentration in blood takes about a week.
“This is much shorter than the time that it takes for protection for a vaccine.
“It is well accepted that there is a gap in interventions for pregnant women; so, this could be a potential use case for a monoclonal antibody,” she says.
Andrews adds that children with anaemia can be a potential use case for a monoclonal antibody.
According to Andrews, while the actual duration of the monoclonal antibody protection has not been established, the target is that a single injection prior to the rainy season will be able to give coverage that is beneficial. (NANFeatures)
