Experimental Malaria Vaccines Show Promising Results

Two experimental malaria vaccinations are not only safe for people, but one of them slowed the replication of the malaria parasite in the bloodstream of clinical trial participants, according to early research using both shots.

More study is needed to fully understand these immunizations and the human immune response because the two vaccines were evaluated in Phase 1 clinical trials. However, excitement has already begun to spread among the malaria research community. If the vaccines work as well in future clinical trials as they did in early pilot studies, the two investigational vaccines could eventually be developed into licensed inoculations. Both vaccines were designed to protect against Plasmodium vivax, one of the most common malaria parasites.

Malaria is a parasite infection caused by any of four Plasmodium protozoan species. P. falciparum, P. ovale, and P. malariae are the other three parasites. Each is only transmitted through the bite of a female Anopheles mosquito, a nocturnal evening flier that is most active between 10 p.m. and 4 a.m. Anopheles mosquitoes typically strike when humans are sleeping.

Female mosquitos require blood to develop their eggs, and when bitten, the malaria parasite easily enters the victim’s bloodstream through the mosquito’s saliva. Malaria is characterized by a high temperature, sweating, chills, muscle aches, headache, and anemia. It can be fatal for certain people, particularly youngsters under the age of five.

“Plasmodium vivax is the second most common cause of malaria and the most geographically widespread, causing an estimated 4.5 million cases in 2020,” writes Mimi Hou, lead author of the vaccine research. She is a pediatric clinical fellow at the University of Oxford in the U.K.

P. vivax is a notable cause of malaria because it is more difficult to control than P. falciparum, the most common malaria parasite that infects the African continent. P. vivax can lay latent in the liver before reviving and infecting the blood.

Hou and colleagues explain in the journal Science Translational Medicine that they planned their clinical trial to assess the experimental vaccines, VAC071 and VAC079, which each addressed separate stages of the parasite’s life cycle. P. vivax Duffy binding protein, or PvDBP, was targeted by both to generate immunity.

Duffy glycoproteins are very complex receptor sites that stipple the surface of red blood cells. These glycoproteins normally function as receptors for cytokines generated during inflammation. However, P. vivax takes advantage of these receptors, exploiting them as entry points and establishing the stage for infection.

The vaccinations were well tolerated in the parallel tests, and the vaccinated individuals demonstrated antibody responses. Trial participants were hospitalized and infected with P. vivax under controlled conditions to provide a thorough grasp of the vaccines’ efficacy. The researchers counted parasites in the blood of 19 vaccine recipients.

Despite the fact that the pandemic interrupted the study project in 2020, COVID did not derail it, and the research resumed in 2021. The researchers discovered that when one of the vaccinations was given in a delayed dosing regimen, it lowered the multiplication rate of P. vivax by 51%.

According to the National Institutes of Health, P. vivax is responsible for 42% of all malaria cases outside of Africa, and the species is widespread in both tropical and subtropical latitudes in Asia, Oceania, and the Americas. This species was also responsible for a number of uncommon, locally acquired malaria illnesses in Florida and Texas this year.

According to the United States Centers for Disease Control and Prevention, 241 million bouts of malaria caused by all four parasite types were recorded in 2020, with 627,000 deaths reported worldwide. 95% of these were in Africa.

Malaria is a difficult disease to treat because the resilient, contagious parasites can thrive in two very different hosts—female mosquitos and people. Despite the differences between these hosts, the parasites are able to complete a complex, multi-stage life cycle in each of them by finding safe harbor.

The three stages of parasite growth are the ookinete, which occurs in the mosquito’s gut; the sporozoite, which is a more mature form that is produced in mosquito saliva when it bites; and the merozoite, which evolves in the human liver. While this describes the life cycle of most malaria parasites, including the sometimes deadly P. falciparum, it does not fully explain infection with P. vivax, which has an additional life-cycle stage.

“Control of P. vivax is more challenging than Plasmodium falciparum due to several factors,” writes Hou. “These include the ability of P. vivax to form dormant liver-stage hypnozoites that can reactivate and lead to relapsing blood-stage parasitemia and earlier production of gametocytes in the blood stage, resulting in more rapid transmission.”

The clinical testing of the two experimental P. vivax vaccines coincides with Ghana becoming the first country to approve another University of Oxford malaria vaccine called R21, created to combat infection with P. falciparum, in April. The pediatric vaccine is intended for children aged five months to three years.

The doses used to immunize volunteers in the present P. vivax vaccine research were based on 10-year-old formulations, but the researchers believes that targeting the Duffy glycoprotein can be done using contemporary vaccination techniques, such as a tailored mRNA platform to deliver the vaccine payload.

Despite hopes for a possible future technique of vaccine distribution, the clinical experiment indicated that old-school approaches sufficed. “No safety concerns were identified with viral-vectored or protein-in-adjuvant vaccines, and no serious adverse events occurred in the VAC071 and VAC079 trials,” Hou stated.

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