The world’s first mass vaccination program against malaria, announced this week, aims to prevent millions of children from catching malaria, and thousands die from this debilitating disease.
The World Health Organization (WHO) has recommended widespread use of the RTS, S / AS01 (Mosquirix) vaccine for young children at greatest risk for malaria in Africa.
Malaria is a big thing
Mosquitoes spread the parasite Plasmodium falciparum from person to person when biting. So until now, our fight against malaria has involved the use of mosquito nets to avoid being bitten and spraying insecticide to kill mosquitoes. Then there are drugs to prevent or treat malaria infection.
However, the parasite has developed resistance to drugs against malaria, and mosquitoes have developed resistance to insecticides. Nevertheless, existing control measures have resulted in a significant decrease in the number of malaria deaths since 2000.
In recent years, however, progress has stalled. In 2019, malaria infection resulted in 409,000 deaths around the world, mostly in children under the age of five and 229 million new malaria cases.
So we need extra tools, such as an effective malaria vaccine, if we are to control the disease globally.
WHO’s recommendation to roll out the Mosquirix vaccine to children at high risk of infection with P. falciparum, which is widespread in Africa, is an important step towards controlling the deadliest of human malaria parasites.
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What did the WHO recommend?
The WHO recommended four doses of the vaccine to children from five months of age.
This recommendation follows the latest results from a pilot program in Ghana, Kenya and Malawi that involved vaccinating more than 800,000 children since 2019.
The program showed that delivery of the vaccine is possible and cost-effective in high-risk areas. It also increased the number of children (to more than 90%) who have access to at least one effort to prevent malaria.
The vaccine has a good safety profile and reduces cases of clinical and severe malaria, which can be fatal.
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What do we know about the vaccine?
Mosquirix is a “subunit” vaccine. This means that it contains only a small part of the malaria parasite, which is produced as a synthetic protein.
This protein is linked to an “adjuvant”, a molecule designed to stimulate a strong immune response.
The vaccine works mainly by stimulating the body to make antibodies against the parasite, neutralizing it and preventing it from entering liver cells. These are the first cells that the parasite invades when it enters the body.
The vaccine also works by helping to mount an inflammatory response when another part of the immune system responds.
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The vaccine is not perfect
The level of protection provided by the vaccine is not ideal. Protection varies with the age of the child at vaccination, with less protection for young infants compared to older children. In the older children (5-17 months old), this averaged about 36% protection against developing clinical malaria over a four-year period.
Protective immunity also declines rapidly over time. This means that regular booster doses will be needed. Alternative immunization plans are also being evaluated.
Nevertheless, the vaccine can still make a significant contribution to malaria control when used in high malaria risk areas and with other control measures.
A modeling study estimated that Mosquirix in sub-Saharan Africa could prevent up to 5.2 million cases of malaria and 27,000 deaths in young children each year.
Why has it taken so long to get here?
Developing a malaria vaccine is challenging. Technically, it is difficult to develop a vaccine against a parasite that lives in two hosts (mosquitoes and humans).
There has also been limited interest from pharmaceutical companies in developing a malaria vaccine.
Although travelers will benefit from a vaccine when traveling to the affected countries, the people most in need of a malaria vaccine live in some of the poorest countries in the world. So there is little financial incentive to develop a vaccine.
Mosquirix is the result of more than 30 years of research and was created through a partnership between GlaxoSmithKline (GSK) and the Walter Reed Army Institute of Research in the United States.
This time frame is not long considering that both the antigen design and the adjuvant system were new.
The Bill & Melinda Gates Foundation and GSK supported further development, including evaluation of the vaccine in clinical trials. Over three decades, they invested about $ 700,000 million to develop the vaccine.
This current version of Mosquirix is not expected to be the latest. Preliminary results for a new modified vaccine, called R21, are encouraging.
Other developing malaria vaccines include whole parasite vaccines. These use the whole malaria parasite that has been killed or altered so that it cannot cause a malaria infection but can still stimulate an immune response.
Passive vaccines are also being investigated. These involve injecting long-lasting antibodies to prevent malaria infection.
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A whole new set of challenges
Meanwhile, the WHO recommendation presents a new set of challenges.
Malaria-affected countries must decide whether to include Mosquirix as part of their national malaria control strategy.
Critical funding decisions from the Global Public Health Community will be needed to enable the vaccine to be widely rolled out to the children who will benefit most from it.
Production capacity for tens of thousands of doses each year, global vaccine supply chains and distribution infrastructure in malaria-affected countries will also be needed.
Finally, each country must maximize vaccine uptake and ensure the implementation of the four-dose immunization plan in order to obtain the full benefit of the vaccine.