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What you need to Know about WHO Recommended Novel RTS,S Malaria Vaccine

By Dr. Nwamaka Osakwe

Are you curious about the new RTS,S malaria vaccine? Learn all about it here and
try out the fun quiz at the end.

After more than a century and billions of dollars, the world finally has a vaccine against malaria.
On October 6, 2021, the World Health Organization (WHO) recommended the RTS,S malaria
vaccine for widespread use.

In 2019, about half of the world’s population was at risk of contracting malaria. In the same
year, there were 229 million cases of malaria and 409,000 malaria-related deaths. 67% of these
deaths occurred in children less than 5-years-old. Half of the malaria-related deaths globally
occurred in six countries — Nigeria (23%), the Democratic Republic of the Congo (11%), United
Republic of Tanzania (5%), Burkina Faso (4%), Mozambique (4%), and Niger (4%).

For many people, the RTS,S malaria vaccine brings fresh hope of ending the scourge of malaria
and making more countries malaria-free.

So, what caused the delay in developing a malaria vaccine?

The malaria parasite is complex, making it difficult for scientists to develop an effective vaccine. In general, scientists do not completely understand the “specific immune response associated with protection” against malaria.

According to the CDC, economic barriers also posed a challenge to malaria vaccine development. The demand for malaria vaccines would come primarily from the regions most affected by malaria. For example, 94% of all malaria cases occur in Africa. However, this is not a “traditional market” and might not attract the interest of pharmaceutical companies who need to make a profit.

History of RTS,S

Scientists at GlaxoSmithKline (GSK) created the RTS,S vaccine, also called Mosquirix, over 30 years ago. Since then, the Bill and Melinda Gates Foundation and PATH malaria vaccine Initiative have supported GSK in developing this vaccine. As a result, more than 500 billion dollars have been spent on research, leading to the historic approval of the vaccine by the WHO.

The phase 3 clinical trial, completed in 2014, was carried out in 11 centers in 7 countries. It was a double-blind, randomized control trial involving 15,459 children in two age groups (infants 6-12 weeks and children 5-17 months). Researchers followed up the infants for a median of 38 months and the children for 48 months. The results showed that RTS,S offered less protection to the infants when compared to the older children. In addition, the protection by the vaccine waned after a year. These findings led to a recommendation for a pilot program.

In 2019, the pilot program to test the vaccine’s efficacy in real-life settings was initiated in Ghana, Kenya, and Malawi. The aim was to see if the results seen during clinical trials were reproducible. The program is still ongoing. However, the findings show that RTS,S malaria vaccine is feasible, cost-effective, and safe.

How does the malaria vaccine work?

During feeding, the mosquito transmits the parasite Plasmodium falciparum into an individual’s
blood. The parasite enters the liver, where it matures and multiplies (the pre-erythrocytic
stage.), then released back into the bloodstream to invade the red blood cells. The entry of the
parasites into the red blood cells is responsible for most of the symptoms of malaria.

Mosquirix prevents Plasmodium falciparum from infecting the liver. By acting at the pre-
erythrocytic stage, Mosquirix protects the host against malaria. Apart from preventing parasite
entry into the liver, the vaccine also sensitizes the immune cells to destroy liver cells infected by
Plasmodium falciparum.

Efficacy

Mosquirix offers partial protection against clinical malaria with an efficacy of 39%. The phase 3
trials showed that it prevented 4 in 10 cases of clinical malaria and 3 in 10 cases of severe
malaria.

When the Malaria Vaccine Technology road map was developed, the aim was to develop malaria vaccines against Plasmodium falciparum which causes most malaria in Africa, and a vaccine against Plasmodium vivax that causes most malaria outside Africa. According to the map, the interim plan was to develop a first-generation vaccine by 2015 with at least 50% efficacy. Mosquirix falls short of this target. But even at 39% efficacy, one modeling study projects that 23,000 deaths can be prevented annually if all the children in endemic countries are vaccinated with Mosquirix. WHO recommends this vaccine to help prevent tens of thousands of deaths and offers Africa a “glimmer of hope.”

It is essential to be aware of the limitations of the malaria vaccine. First, it does not protect against all forms of malaria. Here are the five species of malaria parasite that cause malaria:

  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malariae
  • Plasmodium knowlesi

Mosquirix only protects against Plasmodium falciparum. To create the vaccine, scientists combined the P falciparum antigen with an antigen from hepatitis B. This combination increases the ability of the vaccine to trigger an immune response. However, since no other malaria antigens are included, the vaccine does not protect against other forms of malaria.

Plasmodium falciparum is the most common mosquito species found in Africa. It is responsible for most of the severe forms of malaria seen. Therefore, an effective vaccine against Plasmodium falciparum would significantly impact the prevalence of malaria in Africa and globally. Although Mosquirix contains the P falciparum antigen, it offers only partial protection at best.

Dosing

WHO approved RTS,S malaria vaccine for children from 5 months of age who live in moderate to high transmission areas. During the trials, RTS,S demonstrated no protection against severe malaria or need for hospitalization in infants between 6 weeks to 12 weeks.

Three initial doses of 0.5ml are given intramuscularly one month apart. A booster dose (4th dose) is given 15 to 18 months after the 3rd dose. During the study, researchers observed that protection against malaria waned over time. They also noted that there had been a non-significant increase in severe malaria among the vaccinated group in the last six months of follow-up. 

Trials are ongoing, investigating the effects of the booster vaccine dose.

Safety

Some safety concerns that emerged during the clinical trial were: 

  • increase in febrile convulsion, 
  • cerebral malaria, and 
  • meningitis among the vaccinated group when compared with the unvaccinated. 

Other side effects were: 

  • fever, 
  • localized pain, and 
  • swelling at the injection site.

Despite these observations, the WHO and the European Medicines Agency (EMA) currently consider the vaccine safe.

Pricing and next steps

GSK, the vaccine manufacturer, has not yet released the price for the vaccine. However, BBC reports that GSK intends to supply the drugs at manufacturing cost + 5%.

The pilot study in Ghana, Malawi, and Kenya is still ongoing. The next step is for other malaria-endemic countries to adopt the vaccine as part of their national program.

Recommendations

The vaccine should be used in addition to other malaria preventive strategies, including:

  • Insecticide-treated nets
  • Insecticides
  • Intermittent preventive therapy for pregnant women
  • Antimalarials

For now, the malaria vaccine is recommended for infants and young children. There is no recommendation for adults or travelers.

Other promising malaria vaccines on the horizon

Several promising vaccines are currently being studied, including: 

  • Pre-erythrocytic vaccines: Similar to mosquirix, these vaccines prevent the malaria parasite from entering the liver or replicating in the liver.
  • Blood vaccines: These reduce replication in the red blood cells. As such, they reduce the density of the parasite in the red blood cells. Consequently, it reduces the severity of malaria in vaccinated individuals.
  • Transmission vaccines: These aim to prevent the maturation of the malaria parasite in the mosquito. By doing that, it prevents malaria from being transmitted to another individual.

Summary

The WHO recommendation of the RTS,S malaria vaccine represents a pivotal moment in the history of malaria. Although the efficacy is 39%, studies show that it will prevent tens of thousands of deaths. In addition, the vaccine is feasible, cost-effective, and safe.

To learn more about the malaria vaccine, click here and here. In the meantime, you can test your knowledge of the malaria vaccine with our quick quiz below.

Nwamaka Osakwe, MBBS, is a physician who loves writing about health and wellness. You can reach her here.

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Take the malaria vaccine quiz: 5 questions.

1. How many doses of the Mosquirix vaccine does WHO recommend?

a. 2

b. 3

c. 4

d. 5

2. WHO recommends the Mosquirix vaccine for children from the age of

a. 5 weeks

b. 5 months

c. 8 weeks

d. 8 months

3. The Mosquirix pilot vaccination program is ongoing in 

a. Nigeria, Ghana, and Tanzania

b. Nigeria, Congo, and Tanzania

c. Nigeria, Ghana, and Malawi

d. Ghana, Malawi, and Kenya

4. The booster dose is given

a. 6 months after the 3rd dose

b. 12 months after the 3rd dose

c. 15 months after the 3rd dose

d. 2 years after the 3rd dose

5. Mosquirix protects against

a. Plasmodium falciparum

b. Plasmodium vivax

c. Plasmodium malariae

d. All forms of malaria

Answer: 1=c, 2= b, 3 = d, 4 = c, 5 = a