Can mosquitoes deliver vaccines against malaria? , health News

Mosquitoes are commonly associated with serious diseases such as malaria, dengue fever and yellow fever. However, researchers at Leiden University Medical Center (LUMC) and Radboud University in the Netherlands may have found a valuable new role for insects: as vaccine distributors.

Their scientists say they have successfully engineered mosquitoes to deliver vaccines that could potentially provide significantly enhanced immunity against malaria.

The World Health Organization’s most recent World Malaria Report showed that an estimated 597,000 people could die from malaria globally in 2023, with African countries bearing the brunt of the deaths – accounting for 95 percent of malaria deaths. It is responsible.

Scientists estimate that more than 240 million malaria cases occur each year around the world. Children and pregnant mothers are most susceptible to this disease.

How does mosquito-delivered vaccine work?

The vaccine uses a weakened strain of Plasmodium falciparum (P. falciparum), the parasite that causes the most deadly form of malaria in humans.

“We have removed a key gene in the malaria parasite, which is still allowing the parasite to infect people but not make them sick,” said vaccinologist Meta Rostenberg., Professor of Vaccinology and Clinical Head of the Center for Controlled Human Infections at LUMC.

Typically, malaria is transferred to humans through the bite of the parasite. The mosquito uses its long, needle-like mouth (called a proboscis) to pierce the skin, injecting its saliva into the bloodstream before sucking the blood. The parasites in saliva travel directly to the liver, where they reproduce rapidly, infecting red blood cells with malaria before they leave the liver. This causes symptoms like fever, chills and sweating.

In the clinical trial, the research team used mosquitoes carrying the modified parasite to deliver the vaccine via bite, mirroring the natural transmission of malaria. The goal: to create a strong immune response in the liver and provide protection against malaria infection.

“Because the gene is turned off, this parasite cannot complete its development in the liver, enter the bloodstream and thus cannot cause symptoms of the disease,” Rostenberg said. “At least that was the theory.”

How were the tests conducted?

The first trial tested an injectable malaria vaccine derived from a genetically modified parasite called PfSPZ GA1. The collaborative study with Sanara, the US-based biotechnology company developing the vaccine, included 67 participants from two cities in the Netherlands (Leiden and Nijmegen).

Results of the study, published in Science Translational Medicine in May 2020, showed that the GA1 vaccine was safe to use and delayed the onset of malaria but did not prevent participants from getting the disease.

In the second trial, participants, none of whom had previously suffered from malaria, received mosquito-delivered versions of two vaccines – GA1 and a modified version of it, GA2. With the GA1 vaccine, the parasite replicates in the liver within 24 hours. With the GA2 vaccine, the parasite reproduces for a longer period of time – up to a week – giving the immune system more time to recognize it and begin fighting it.

Researchers first tested the GA2 vaccine dose on participants to determine its safety and tolerability. The participants were then divided into three groups: two groups received the GA1 and GA2 vaccines tested respectively, and one group was given a placebo.

In each of three sessions, participants received 50 mosquito bites: eight by mosquitoes infected with GA1, nine by mosquitoes infected with GA2 and three by non-infected mosquitoes. Participants who completed the vaccination phase suffered five bites from mosquitoes carrying the malaria parasite.

What were the results?

The results of the study were published in the New England Journal of Medicine in November.

According to the trial, 13 percent of the GA1-infected group and 89 percent of the GA2-infected group developed immunity to malaria. No one in the placebo group developed immunity.

Is further research needed?

Experts said, because the sample size of the clinical trial was small (20 participants), the GA2 vaccine still needs to be tested in larger studies.

More research is also needed to determine how well the GA2 vaccine boosts the immune system over the long term and whether it can protect against different strains of the malaria parasite in areas where the disease is common.

“Using the mosquito as a vector is an easy and fast way to spread malaria sporozoites,” Rostenberg explained. “Of course, this is not sustainable in the long term, and so the product will have to be developed into a vialed vaccine to be introduced in Africa.”

“Mosquitoes could not be implemented to deliver vaccination on a large scale. “This is possible only in the context of clinical trials.”

Have insects been used to deliver vaccines before?

Japan, 2010

In 2010, Japanese scientists genetically modified mosquitoes to create a vaccine against leishmaniasis, a parasitic disease commonly spread by sandflies in their salivary glands. During a mosquito bite, the vaccine was expressed through its saliva.

The study showed that rodents bitten by “flying vaccinators” developed antibodies against the parasite. However, researchers have not yet determined whether the resulting immune response is sufficient to prevent infection.

“After being bitten, protective immune responses are induced just like traditional vaccination, but without any pain and without any cost,” lead researcher Shigeto Yoshida of Jichi Medical University said in a statement.

United States of America, 2022

In September 2022, a study involving 26 participants in Seattle, Washington explored the potential of mosquitoes as vaccinators.

Similar to a trial conducted in the Netherlands, mosquitoes served as carriers of malaria-causing Plasmodium parasites that were genetically weakened using CRISPR gene-editing technology. This was the first significant clinical trial to use mosquitoes as a direct vaccine delivery system with genetically modified parasites.

Participants were first given a malaria vaccine and then given the malaria virus to see if the vaccine would prevent them from getting malaria.

The mosquito-delivered vaccine was 50 percent effective and seven of 14 participants got the disease.