A vaccine breakthrough may finally restrain this insidious disease

The speedy development of Covid-19 vaccines was nothing short of stunning.

What usually takes 10 to 15 years happened in a single year. The world saw in real-time what could be accomplished when scientists are given the resources to push their work into uncharted territory. Science seemed posed to tackle the challenge.

Yet, nearly half of the world’s population is faced with a lethal pathogen for which there’s no vaccine or cure. It kills four times as many children as cancer. It’s malaria, and it’s one of the most deadly diseases in the world. It has roughly the same global health impact as HIV, yet receives about five percent of the funding.

The results of a trial of a vaccine candidate, published Wednesday in Nature, are promising — a critical step toward malaria inoculation.

However, experts say malaria poses an even greater, more complex challenge than the novel coronavirus. To see real progress towards malaria eradication, ongoing scientific breakthroughs need to be paired with attention and funding.

Patrick Duffy is Chief of the National Institute of Health’s Laboratory of Malaria Immunology and Vaccinology and one of the lead authors of the study. “[Malaria] has been around forever, but nobody treats it like it's an emergency,” Duffy tells Inverse. “It is an emergency. It's an emergency every year.”

What you need to know first — Malaria is caused by a parasite and spread by mosquitos in tropical and subtropical areas of the world. Among the most affected by the disease are children and pregnant women, as well as travelers and migrants to areas where the disease is active.

When someone is bitten by a mosquito carrying the parasite that causes malaria, the parasite enters the person’s bloodstream and travels to the liver, where it sets up camp. When the parasites mature, they leave the liver and infect red blood cells.

Left untreated, the disease can be fatal. The World Health Organization estimates that 94 percent of malaria deaths occur in Africa–most commonly in children under the age of five.

Brandon Wilder is a malaria researcher and Assistant Professor at Oregon Health and Science University's Vaccine and Gene Therapy Institute, and was not involved in the new study. Wilder tells Inverse that there are three main malaria vaccine candidates currently undergoing late-stage trials:

• Mosquirix: This is similar to the Covid-19 Novavax vaccine. You take a protein from the pathogen and mix it with something designed to anger the immune system, which then produces antibodies that attach to the parasite and prevent it from entering a cell — in this case, the liver which is where the parasite first begins infection. Wilder says Mosquirix looks to be about “30 to 50 percent effective,” though immunity wanes over time.
• R21: this candidate is also similar to the COVID-19 Novavax vaccine and targets the same parasite protein, but has been shown to create a higher level of antibodies than Mosquirix: it reduces disease up to 75 percent for a full year, the first time any vaccine has reached that threshold.
• Sanaria’s PfSPZ vaccine: Sanaria is a biotech company. This vaccine is different from the other two in several respects: First, there are three types. All are created using a live parasite from the mosquito’s salivary gland. Where they differ is how the parasite is weakened: For PfsPZ, the virus is irradiated. PfsPZ-GA1 uses a genetically weakened parasite that's then injected into a person. Meanwhile, PfSPZ-CVac is injected into a person who is on malaria drugs.

Duffy and his colleagues are working on PfSPZ — specifically, PfSPZ-CVac.

In contrast to Mosquirix and R21 which use antibodies to keep the parasite out of the liver, the PfSPZ vaccine can also work by targeting the parasite after liver infection with T-cells. This appears to do a better job of actually stopping all parasites from infecting rather than just keeping infection low enough to prevent disease.

What’s new — In a trial of 56 healthy adults, the researchers injected participants with PfSPZ-CVac.

The participants were also taking either pyrimethamine, which kills liver-stage parasites, or chloroquine, which kills blood-stage parasites. (You might remember chloroquine from the early days of the Covid-19 pandemic.)

What they found — The researchers found higher doses of the parasite (while keeping the dose of the drugs constant) were the most effective.

The highest dose resulted in a vaccine efficacy of up to 87.5 percent, surpassing the R21 vaccine.

The team subsequently tested the vaccine against a different strain of the parasite: the 7G8 strain, which is commonly found in Brazil. Testing the vaccine in six individuals resulted in 100 percent protective efficacy against 7G8 for up to three months.

These findings are particularly exciting because one of the biggest challenges with malaria is finding a vaccine that works against the many, ever-evolving strains. While it’s not a guarantee that PfSPZ will work against all strains, it’s hopeful.

What we still don’t know — Duffy cautions that people that live in the affected areas are different than people at the NIH Clinical Center.

“Their diet is different, they have other infectious diseases, and there's very good evidence that if somebody has any parasites in their bloodstream, it will negatively impact getting the good immune response to this vaccine,” he says.

But with a disease as stubborn and tricky as malaria, any positive outcomes in vaccine development are a crucial step forward.

If there was more focus on and funding for malaria, those steps might look more like leaps, Wilder says.

“If there was an Operation Warp Speed for malaria, our chances of having an effective vaccine that we could use for elimination in five years would go way up,” he says

But because it’s not a problem in the United States, and affects primarily poor countries in Africa, focus and funds are hard to come by.

“At the current rate, it is hard to have much hope for anything before 10 years,” Wilder says. “That’s perhaps 4 million children that will die in that time frame and about 2 billion infections.”

Abstract: The global decline in malaria has stalled1, emphasizing the need for vaccines that induce durable sterilizing immunity. Here we optimized regimens for chemoprophylaxis vaccination (CVac), for which aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites (PfSPZ) were inoculated under prophylactic cover with pyrimethamine (PYR) (Sanaria PfSPZ-CVac(PYR)) or chloroquine (CQ) (PfSPZ-CVac(CQ))—which kill liver-stage and blood-stage parasites, respectively—and we assessed vaccine efficacy against homologous (that is, the same strain as the vaccine) and heterologous (a different strain) controlled human malaria infection (CHMI) 3 months after immunization. We report that a fourfold increase in the dose of PfSPZ-CVac(PYR) from 5.12 × 104 to 2 × 105 PfSPZs transformed a minimal vaccine efficacy (low dose, 2 out of 9 (22.2%) participants protected against homologous CHMI), to a high-level vaccine efficacy with 7 out of 8 (87.5%) individuals protected against homologous and 7 out of 9 (77.8%) protected against heterologous CHMI. Increased protection was associated with Vδ2 γδ T cell and antibody responses. At the higher dose, PfSPZ-CVac(CQ) protected 6 out of 6 (100%) participants against heterologous CHMI. All homologous (4 out of 4) and heterologous (8 out of 8) infectivity control participants showed parasitaemia. PfSPZ-CVac(CQ) and PfSPZ-CVac(PYR) induced a durable, sterile vaccine efficacy against a heterologous South American strain of P. falciparum, which has a genome and predicted CD8 T cell immunome that differs more strongly from the African vaccine strain than other analysed African P. falciparum strains.