Building a better malaria vaccine: Mixing the right cocktail

December 26, 2013
Human red blood cells are surrounded and invaded by malaria parasites (purple). Credit: Sheetij Dutta

A safe and effective malaria vaccine is high on the wish list of most people concerned with global health. Results published on December 26 in PLOS Pathogens suggest how a leading vaccine candidate could be vastly improved.

The study, led by Sheetij Dutta, from the Walter Reed Army Institute of Research, USA, and colleagues, focused on a protein called AMA1 needed by the Plasmodium falciparum parasite to invade blood cells and cause disease. Study results suggest that a cocktail of AMA1 proteins from only a few different strains can overcome major limitations of an earlier designed version of AMA1-based vaccines.

The challenge with the malaria parasite in general and its AMA1 surface protein in particular is that both exist as multiple strains. Using AMA1 in a readies the human immune system for subsequent encounters with the parasite, but when such a vaccine was previously tested in humans, it was effective mostly against one particular P. falciparum strain. To explore the potential for a more broadly protective vaccine, the scientists tested different cocktails of AMA1 from different parasite strains for their ability to elicit a diverse range of that are active in parasite inhibition assays. They confirmed that a cocktail of AMA1 proteins from three different parasite strains was better than one or two, and one they call Quadvax, which contained AMA1 proteins derived from four different strains, led to an antibody response that was broader than the sum of strain-specific antibodies elicited by the four individual strains. Moreover, Quadvax-elicited antibodies inhibited a range of parasites, including many strains that were different from those in the Quadvax mix. In different laboratory tests, Quadvax-induced antibodies inhibited the growth of 26 different parasite strains, and the scientists suggest that "the combination of four AMA1 variants in Quadvax may be sufficient to overcome global AMA1 diversity".

Besides varying a lot from strain to strain, AMA1 also contains less variable (conserved) exposed parts (so-called ) on its surface. The researchers found that vaccination with Quadvax yielded not only antibodies against the variable epitopes, but also against more conserved epitopes of the AMA1 protein. Such antibodies were not seen when using individual strains for immunization, but Quadvax appeared to enhance the immunogenicity—the ability to provoke an antibody response—of these conserved parts of the protein. Since the epitopes are identical across strains, the resulting antibodies are broadly active rather than strain-specific.

The scientists conclude "we had set out to study broadening of antibody responses achieved by mixing AMA1 proteins and were surprised and delighted to find not only greater variety of strain-specific antibodies but also increased antibodies against conserved epitopes were induced by the Quadvax. Perhaps even more exciting, when mixed, combinations of these antibodies were synergistic in their broad inhibition of many parasite strains. Novel conserved epitopes described here can be targets for further improvement of the vaccine. Most importantly, our data strongly supports continued efforts to develop a blood stage vaccine against malaria".

In spite of the extreme variability, a vaccine containing only a few diverse AMA1 , the scientists hope, could provide universal coverage by redirecting the immune response towards conserved epitopes. The next steps will be to test human-use formulations of Quadvax in primate models and in a human blood-stage challenge model.

Explore further: Multiple malaria vaccine offers protection to people most at risk

More information: Dutta S, Dlugosz LS, Drew DR, Ge X, Ababacar D, et al. (2013) Overcoming Antigenic Diversity by Enhancing the Immunogenicity of Conserved Epitopes on the Malaria Vaccine Candidate Apical Membrane Antigen-1. PLoS Pathog 9(12): e1003840. DOI: 10.1371/journal.ppat.1003840

Related Stories

Improving human immunity to malaria

August 1, 2012

The deadliest form of malaria is caused the protozoan Plasmodium falciparum. During its life-cycle in human blood, the parasite P. falciparum expresses unique proteins on the surface on infected blood cells.

Australian researchers close in on malaria vaccine

July 2, 2013

Australian researchers said Tuesday they were closing in on a potential vaccine against malaria, with a study showing their treatment had protected mice against several strains of the disease.

Malaria, toxoplasmosis: Toward new lines of research?

October 10, 2013

A study realized by teams from the Institut Pasteur, the Institut Cochin and the Wellcome Trust Centre for Molecular Parasitology of the University of Glasgow, could redefine part of the present lines of research toward a ...

Recommended for you

We've all got a blind spot, but it can be shrunk

August 31, 2015

You've probably never noticed, but the human eye includes an unavoidable blind spot. That's because the optic nerve that sends visual signals to the brain must pass through the retina, which creates a hole in that light-sensitive ...

Biologists identify mechanisms of embryonic wound repair

August 31, 2015

It's like something out of a science-fiction movie - time-lapse photography showing how wounds in embryos of fruit flies heal themselves. The images are not only real; they shed light on ways to improve wound recovery in ...

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

EnricM
3 / 5 (1) Dec 28, 2013
The tragic part of it is that if they succeed in creating an effective malaria vaccine is that children saved from dying from malaria in Africa will die later from starvation or as a result of war.
Does it make sense to fight against the mechanisms that keep the human plague at bay?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.