Malaria hit: two drug-attenuated vaccines induce high levels of protection

An international group of scientists has developed a new strategy against malaria with promising results.

One of the mosquitoes that transmits malaria.

One of the greatest difficulties for the development of the vaccine against malaria is that there are no appropriate animal models and, for this reason, it is necessary to perform clinical trials in endemic populations. Pregnant women and children in these places are the groups most vulnerable to the disease.

The bite of mosquitoes infected by the parasite Plasmodium falciparum spreads the disease through spore-like forms called sporozoites, which manage to enter the liver of the infected person and replicate within cells called hepatocytes. Next, many thousands of infectious parasites are released into the bloodstream, where they infect red blood cells, multiply further, and cause disease.

A team led by Patrick Duffy, a scientist at the US National Institute of Allergy and Infectious Diseases (NIAID), has managed to immunize 56 healthy adult volunteers with chemically weakened infectious sporozoites.

“This is a live parasite vaccine. That is, when we inoculate it they are not attenuated. The way we manage to weaken it is that people who are vaccinated receive drugs and it is these drugs that attenuate the parasite”, Duffy tells SINC.

The trial consisted of administering the vaccine to, days later, receive a dose of pyrimethamine or chloroquine, two prophylactic drugs that kill hepatic and blood phase parasites, respectively. The results are published in the journal Nature.

“The activity of the vaccine is due solely to the immune response that develops The administered drugs do not specifically contribute to long-term protection”, explains the researcher.

The scientists evaluated the efficacy against the homologous strain –the same as the vaccine– and a heterologous one –a different strain– against controlled human malaria infection three months after immunization.

“The parasite we use as a vaccine – the NF54 strain – has been studied since the 1970s and is well known in Africa. In this way, we know that it is very sensitive to the two drugs administered. It has also been used for years to do what we call controlled infections of human volunteers,” says Duffy.

The higher the dose, the more effective

The team evaluated the effect of different vaccine dose. “This implies that we change the dose of the parasite, but we continue to use the same amount of the drug,” adds the expert. Thus, higher doses were associated with increasing levels of its effectiveness. In this sense, an efficiency of up to 87.5% was achieved.

Regarding responses to a different strain of the parasitethe combination with a high dose of chloroquine achieved 100% infectious sporozoite immunization protection against the 7G8 strain, found in Brazil, in six individuals for up to three months.

“We were surprised to see the high level of efficacy against a South American parasite. Really, the protection exceeded our expectations”, affirms the researcher. This call show heterologous protection is important because an effective vaccine must protect against a diverse range of strains of P. falciparum that circulate naturally.

“We think it should work well against many variants in Africa, because the South American strain is very different, and yet people were protected,” continues the scientist. Currently, Duffy collaborates with the University of Bamakoin Mali, to test efficacy in a community that has intense seasonal transmission of malaria in adults.

“As with any research product, we need to expand the number of people in the trials and the focus of malaria infection in a controlled human group. Now, we need to test it in communities that are naturally infected. We expect those results to be available later this year,” she says.

A fight against the stagnant disease

According to the authors of the research, the global decline in malaria has stalledhighlighting the need for vaccines that induce long-lasting sterilizing immunity.

“There has been a huge investment in distributing tools to control malaria. From ensuring that mosquito nets reach the communities, to ensure that drug stocks are available. It has been a global effort. However, it has now stopped and I think it reflects the limits of existing instruments,” says Duffy.

But, in addition, another concern is that the mosquitoes are becoming more resistant to the insecticides that are used and also the parasites to the drugs that are used to combat it.

“The problem is most serious in African countries that have the highest burden of malaria. In fact, in some of them the situation has regressed and malaria has increased”, concludes the scientist.

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