Why the RTS,S malaria vaccine is such a tease

Continuing from Monday’s post, IMP graduate student Taryn McLaughlin explains why the most advanced malaria vaccine is actually not that great.

Malaria has plagued humans for thousands of years. And while we have known the causative agents of the disease- for 150 years, malaria remains scientifically frustrating. In fact, one of the most common treatments for the disease is simply a derivative of a treatment used in ancient China.

One of the most frustrating features is that there is no sterilizing immunity. In other words, for many diseases once you are infected with the microbe responsible, you develop an immune response and then never get the disease again. Not so with malaria. Compounded with terrible treatment and the impracticality of ridding the world of mosquitos, a vaccine sounds like pretty much our only hope. And yet this has been scientifically challenging and unsuccessful for many many reasons.

In fact a number of vaccine candidates have come along in the last few decades that have seemed SO promising only to go on and break our hearts in clinical trials. The most recent of which is a vaccine that goes by the name RTS,S (named for the different components of the vaccine).

As a quick refresher, Plasmodium enters the body via mosquitos as a sporozoite. It then migrates through the skin going into the blood and eventually making it’s way to the liver. Here it goes inside liver cells where it replicates and turns into merozoites (such that one sporozoite becomes thousands of merozoites). This stage of the disease is asymptomatic. Some time later, all those merozoites burst out of your liver cells causing mayhem and invading your red blood cells. Here, they once again replicate and metamorphose. Fun times. Anyways, during the last stage, some of those plasmodium become gametes which get eaten by mosquitos thus completing the life cycle.

This is important in understanding the vaccine strategy of RTS,S and where protection from this vaccine falls apart. RTS,S only represents one protein- CSP- which is present on only one stage of the life cycle (the sporozoite) on only one species of Plasmodium. In theory this is totally fine because if you can get the body to kill all the sporozoites then it’s still a win. In fact, if the vaccine is effective this is even better than targeting later stages because then the infection is stopped prior to all symptoms. (This is why the irradiated sporozoite vaccine from the 60’s was so effective, if impractical.) But when it isn’t effective then you’ve completely lost the battle. If you miss even one sporozoite, that sporozoite can cause full blown severe malaria due to the exponential replication of the parasite. Which is why RTS,S is a tease.

Depending on how you break down the data, you can argue that the vaccine was anywhere from 17-50% effective. Not only is this efficacy low (compared to let’s say 95% for MMR) but it’s based on clinical malaria as the end point. In other words, it was considered a success as long as you didn’t become clinically ill. This is an important distinction to make because it means that those that were “protected” may have still been infected and experienced symptoms. They just didn’t get the nasty version of malaria.

Furthermore, the efficacy rate was lowest in groups that were vaccinated as babies. This is disheartening because babies and small children are the most likely to develop and die from malaria when infected. Also, the protection waned over time such that a year after the children in the study received their vaccination they were once again susceptible to infection and disease.

The RTS,S regime requires 4 separate shots (three primes and one boost) which is on the impractical side. So overall, not great. Why then are people SO stoked about it? In short, because it’s the first malaria vaccine to make it this far in clinical trials. People are really unwilling to give up on it because it’s been the most promising solution. As such, it has turned into quite a heated debate.

As it stands there are three camps duking it out about what to do with RTS,S from here on out. The first says roll it out in massive doses because it’s better than nothing and we need serious help abroad. The second says toss it out and let’s start over. There are better candidates in early phases and who knows what you will do to the parasite population by introducing a vaccine.

The third needs more data. The WHO falls in the third camp and so that camp seems to be winning the debate. As it stands, the vaccine is in fact licensed, but there are no plans to mass administer it. Instead there are plans to test the vaccine in yet more pilot studies in toddlers throughout malaria endemic regions. So I suppose in the meantime, we must be patient. Not my strong suit personally. But after all, we’ve spent thousands of years dealing with these parasites, what’s a few more decades eh?

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Posted on by Quinn Eastman in Immunology Leave a comment

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Quinn Eastman

Science Writer, Research Communications qeastma@emory.edu 404-727-7829 Office

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