Malaria Vaccine With Three Genes Altered Passes Phase 1 Human Trial

Highlights

• A malaria vaccine that includes plasmodium with three genes knocked out was trialed.
• The antibodies that were produced with the human subjects successfully treated the infection
• The vaccine was provided using mosquitoes in a closed environment

A weakened form of the malaria parasite has been found to induce a strong immune response, paving the way for a malaria vaccine soon. The first time-in-human phase 1 study was conducted on 10 healthy volunteers. The antibodies that were formed in the volunteers were found to protect mice that were infected with malaria. Gene Therapy

The malaria parasite was mellowed down by altering three genes that were critical for liver function and then tested for antibody production. Malaria is caused by a parasite and transmitted by mosquitoes; nearly half of the world population is at a risk for malaria.

In the year 2015,

• 214 million people were estimated to be affected with malaria
• It led to 584,000 deaths worldwide

The vaccine that is currently considered to be the most clinically advanced, comprises of parts of fragments of the parasite responsible for the infection. This produced an antibody response but was found to be only partially protective.

Another vaccine that is also available contains the whole parasite but is attenuated, though it is found to be effective, there is a potential for the malaria infection to be caused which has led to the vaccine posing serious health challenges.

Dr. James Kublin and colleagues developed genetically altered parasites by knocking three genes out in Plasmodium falciparum, which restricts its development to only in the liver. This prevents the spread of the infection to the blood, which is the stage of the disease that gives rise to classic malaria symptoms.

Vaccine Administered through Mosquito Bites

Advertisement

The malaria vaccine GAP3KO was administered through the bite of mosquitoes in a closed environment. The study participants developed strong protective antibodies against the malaria parasite but did not show any symptoms of the disease nor was there any sign of the infection in the blood.

The antibodies that were developed in the study participants were then transferred into mice that were humanized. The antibodies were found to block the malaria infection within the liver. The next step is to trial the GAP3KO vaccine in a phase 1b trial controlled malaria infection.

Advertisement

Malaria

Malaria is an infection that is characterized by acute febrile illness and the symptoms of the disease are found 7 days after the infective bite of a vector.

The initial symptoms are fever, chills, headache and vomiting. It is difficult to discern from the initial symptoms if the condition is malaria. It is important to treat the condition within 24 hours as the infection could progress and lead to severe illness, which could even lead to death.

Children who develop this condition are often found to suffer from severe anemia, cerebral malaria or respiratory distress associated with metabolic acidosis.

Multi-organ infection could also occur in adults and is a major form of complication. It has been found that in areas that are prone to malaria, endemic to malaria, there is a mild immunity that is developed where the infection could remain asymptomatic. It will not provide complete immunity but it renders a partial immunity. This is why children in such regions are at a higher risk for the infection with more serious symptoms.

Causes for Increased Spread of Infection

The transmission of the virus is more intense in regions where the mosquito vector has a longer lifespan as this allows the plasmodium parasite to complete its life cycle. Some mosquito species prefer to bite animals rather than humans, which is advantageous for people living in that area. Mosquitoes with a long lifespan and with a strong tendency to bite humans are found in Africa, which is why 90% of malaria occurs in Africa.

Climate also plays an important role in determining the number of mosquitoes that will survive. Changes in temperature, whether it is raining, and availability of stagnant water are all important for the spread of the infection via mosquitoes.

Importance of Malaria Vaccine

A malaria vaccine is not only important for people who live in the region prone to malaria but also to travelers. In the United States, 1500 to 2000 cases are reported every year due to the infection carried by travelers. Immigrants, who could be second or third generation could return to their ancestral home during vacations and bring back the infection. In order to prevent the entry of infection, a successful vaccine would encourage mandatory use before people travel to areas that are prone to malaria.

Pregnant women are susceptible to infection by the malarial parasite and it leads to 8% to 15% low birth weight of the fetus, lowering its chances of survival. A vaccine would aid in protecting women who wish to get pregnant soon.

A vaccine for malaria has been long sought after and this current vaccine that includes the malarial parasite with three genes knocked out might just be what the doctor will order soon for protection against malaria.

References:

1. Malaria - (http://www.who.int/mediacentre/factsheets/fs094/en/)
2. Malaria Facts - (https://www.cdc.gov/malaria/about/facts.html)

Source-Medindia