Carlota Dobaño is Associate Research Professor and Head of the Malaria Immunology Group at ISGlobal
I am sure you have heard various announcements recently about new and promising malaria vaccines that are achieving high levels of protection. However, as we have been reading articles in the press for some years now about malaria vaccines that are “almost ready”, you may be asking yourself “Hasn’t a malaria vaccine already been discovered?”.
We still have no vaccine to protect people from malaria, that kills nearly half a million people every year
And the answer to that question is no. We still do not have a vaccine to protect people from this disease that kills nearly half a million people every year, particularly in vulnerable populations (children) in low-income countries. The statistics can be found in the World Malaria Report 2016, published by the World Health Organisation (WHO). It is because there is no vaccine that people travelling to areas where malaria is endemic are advised to take preventive medicines and protect themselves from contact with mosquitoes using insecticides, insect repellents and bednets.
There is not just one but several vaccines in the experimental pipeline
Furthermore, there is not just one but several experimental vaccines in the pipeline. While some of them have demonstrated acceptable levels of efficacy, none has yet completed all the development phases (safety, immunogenicity, efficacy) and been licensed for sale. Since the Plasmodium parasite that causes malaria is a biologically complex organism, finding the right vaccine is proving extremely difficult and researchers are currently working on several different candidates, each one of which targets a different life stage of the parasite.
Types of Vaccines
The RTS,S/AS01E vaccine is the most clinically advanced candidate (registered as Mosquirix), with the involvement of ISGlobal and CISM
One strategy researchers are investigating is the induction of an immune response (our defence mechanism) using a single protein or antigen (subunit vaccines) administered in different formulations. This is the strategy used in the RTS,S/AS01E vaccine, the most clinically advanced candidate (registered as Mosquirix). ISGlobal has been involved in the development of RTS,S for many years, working together with the Manhiça Health Research Center (CISM) in Mozambique. Some of the vaccines of this type— including RTS,S—are designed to prevent the parasite from infecting the liver before the patient develops symptoms. Others are designed to reduce disease severity, targeting the blood-stage parasites. Finally, the vaccines most prioritised in the context of malaria elimination (MalERA) are those designed to interrupt human-to-mosquito transmission of the Plasmodium parasites.
Another type of malaria vaccine that has hit the headlines recently (GAP3KO, PfSPZ and PfSPZ-CVac) contains whole parasites and is intended to induce a broader and more potent immune response. Some of these vaccines containing parasites attenuated by irradiation, coadministration with drugs or genetic modification, have achieved remarkable results in two studies involving a small number of European and North American adults, in which they proved to be safe and prevented infection in 100% of the volunteers. Despite this success, these very promising vaccines still have to overcome a series of obstacles before they can be validated and put to use. For example, work is still needed to optimise the number of doses, the quality and quantity of the inoculated parasites (currently very high), the route of administration (currently intravenous), and the production, conservation and distribution of the vaccine (currently dependent on liquid nitrogen).
ISGlobal Malaria Immunology Group
Challenges in Vaccine Development
All vaccines have advantages and disadvantages. None is perfect and the most likely solution ultimately will be that malaria control and elimination programmes will use a combination of the most effective vaccines, which will complement each other. All vaccines also share a number of limitations:
- Duration of immunity. The current vaccine candidates still have to demonstrate an acceptable duration of protection that will make frequent revaccination unnecessary.
- Parasite diversity. The multiplicity of life-cycle stages and parasite strains means that immunisation must be multi-stage, multi-species, and multi-strain to maximise antigen cover and minimise the evasion mechanisms that cause failures.
- Lower immunogenicity and efficacy in target populations: Africans and children.
- Poor understanding of the vaccine-induced immune responses responsible for the protection afforded by vaccination.
Although major advances have been made and experimental studies have shown that the induction of total immunity to infection with Plasmodium is possible, a huge effort by the scientific community is still needed to fill in the gaps in our understanding of current vaccines. Our priority in the Malaria Immunology Group at ISGlobal is to identify the mode of action of these vaccines, which—somewhat surprisingly—is still unknown!
A huge effort on the part of the scientific community is still needed to fill in the gaps in our understanding of current vaccines
We do not yet understand why the RTS,S vaccine or the attenuated parasite vaccines work in some people and not in others. In other words, we do not know what immune responses are induced in people who are protected and in people who are not, or understand the immunological mechanisms that provide protection against malaria. Without this basic information, there is no rational way to improve the second generation of vaccines and to ensure greater efficacy and more prolonged immunity. An understanding of the mechanisms is essential if we are to create vaccines more likely to work in the population in which immunisation has so far been less effective—children in Africa—precisely the population in most need of protection.