The challenges of an effective malaria vaccine

Why is it difficult to produce a malaria vaccine?


So why is it taking so long to develop a malaria vaccine when new vaccines are developed all the time? There approximately 225 million cases of malaria globally and as many as 800,000 resultant deaths per year; most of the victims are children under the age of five years.

There have been several hurdles that have to be jumped over in order for a vaccine to reach end-stage development. There have been few willing to undertake its development and the fact that the development of a vaccine against a parasite is extremely complex; the malaria parasite has a complex lifecycle and the human immune system response is complex and not well understood.

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Malaria is a parasitic infection borne by mosquitoes. The organism that causes malaria is not a virus or a bacterium, it is a single-celled parasite which invades and multiplies in human red blood cells and the intestine of the mosquito.

The malarial parasite has been in existence for at least 50,000 and they have managed to do this by constantly changing and mutating; these constant mutations have resulted in more drug-resistant parasites and more insecticide-resistant mosquitoes. The development of a malaria vaccine has the potential to save countless lives and could help to ultimately eradicate this deadly organism.


The lifecycle of the plasmodium parasite

Malaria differs from other infectious diseases for which vaccinations have been developed in that the parasite which causes malaria passes through ‘multiple life stages’. This presents challenges to the people developing vaccines. There are three stages of the plasmodium life cycle:

  1. Pre-erythrocytic stage - this is better known as the liver stage or the stage before the parasite infects the red blood cells.

  2. Erythrocytic stage - which is the stage when the parasite is infecting red blood cells.

  3. The sexual stage - in this stage the parasite has been taken up by a mosquito and is reproducing in its gut.

The way the stages work is that the infected mosquito bites a human and the parasite goes directly to the liver. The parasite matures in the liver and will then enter the red blood cells; when it is ready to infect another host it will be sucked up by another mosquito and reproduce in the mosquitoes’ gut.


Current research

Research is being carried out into three different types of vaccines, each of which is aiming to disturb a different stage of the life cycle:

  • Pre-erythrocytic stage vaccines - these vaccines target the infectious stage. The aim is to either prevent the parasite (known as sporozoites at this stage) from entering the liver or alternatively to destroy infected liver cells. The time frame for this is difficult because once infected, the sporozoites can reach the liver in less than an hour; as a result, the immune system has very little time to eliminate the parasite. Currently, there is one pre-erythrocytic vaccine showing promise and it is in stage three trials; it is the RTS,s vaccine.
  • Erythrocytic stage vaccines - these vaccines target the blood stage and the aim is to prevent the rapid invasion and asexual reproduction of the parasite in the red blood cells. Symptoms appear at the blood stage of the disease and it is also the most destructive stage to the sufferer as a result of the bursting of large numbers of red blood cells occurring at this time. A blood-stage vaccine can only hope to reduce the number of parasites (known as merozoites at this stage) infecting the red blood cells. So far there have been no successful blood-stage vaccines.
  • Sexual stage vaccine - this vaccine aims to target the sexual production of the parasite that occurs in the mosquito gut. This approach is known as a ‘transmission-blocking vaccine’. This is an indirect approach to the problem in that it aims to kill the vector, the mosquito, in order to prevent further spread of the disease and does not aim to protect the individual.

Many scientists believe that the next step will be to combine these approaches in order to develop a vaccine. This cannot be pursued until vaccines for each stage have shown their own efficacy


Malaria vaccine pilot in Africa - RTS, S

The RTS, S mentioned above has taken 30 years to reach this point in its development. To date, it is the only vaccine that has demonstrated a degree of efficacy in preventing the incidence of malaria in children. In trials, it was shown to prevent approximately 4 in 10 malaria cases including 3 in 10 cases of life-threatening severe malaria cases.

Ghana, Kenya, and Malawi are taking part in the pilot and aims to reach approximately 360,000 per year across the three countries. This is not a vaccine trial but a vaccination program aimed to define more accurately its efficacy and safety.



I think that it is fair to say that we are a long way down the road towards developing a totally safe and efficacious vaccine for malaria but still have a little way to go.

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