Malaria vaccine fever

On October 19, 2011, in Gates Foundation, immunology, malaria, vaccination, by Karen Grepin

I unfortunately had to miss the Malaria Forum being hosted by the Gates Foundation in Seattle this week. For the past 2 weeks, my household has been suffering from NYCPV – the dreaded New York City Playground Virus – and when the time came to get on my flight I was voiceless and feverish. I figured I should spare my colleagues my presence…and my germs.

While there was lots of good stuff discussed at the Forum this week, most of it has now been overshadowed by the announcement of interim phase III trial results of a subunit vaccine for malaria, known as RTS,S. The interim results line up with what most people who have been following the saga of this vaccine over the years would have expected, a roughly 50% protective efficacy against cases of malaria and a roughly 35% reduction in cases of severe malaria in young children roughly 12 months after the vaccines were given (I prefer the intention-to-treat results, not the higher per-protocol results that many in the press have been reporting instead). This is clearly very good news…and something no doubt worth celebrating.

That said, and unlike the rest of the world which seems to have gone crazy celebrating this news, I can’t seem to get too excited about these results, at least for now. Sure from a scientific perspective this is really groundbreaking: we now have a vaccine against malaria that has shown to be somewhat effective in a phase III trial. It is also a vaccine against a parasite, which itself is a big accomplishment. Peter Hotez released a press release earlier today in which he describes this news as the equivalent to walking on the moon in terms of its scientific contribution. Wow.

But as a public health professional, I just don’t think that enough new evidence has been presented for us to think that we found a “game changer” when it comes to malaria prevention and control. The real question, at least in my mind, that is relevant in this discussion is: does this vaccine provide any real lasting immunological protection in the target populations? The interim study was not set up to address this question. The actual full study was but, and I am not entirely sure why, the interim results were published anyway years before the real results of this study are going to be known. I am not the only one who questions the merits of this approach, in the accompanying editorial in the NEJM by Nicolas Witte, a true expert in this area, said “there does not seem to be a clear scientific reason why this trial has been reported with less than half the efficacy results available”. But of course we all know it is not always just science that drives most scientific discussions.

What this study showed was that up to 12 months there was a reduction in the cumulative number of cases of clinical and severe malaria in those receiving the treatment vs. those that did not. Unlike traditional vaccines, immunization in this case does not prevent infection per se, it might just delay it or delay the clinical manifestation of the symptoms. We don’t know. Even this study showed that the efficacy of the vaccine had already started to wane before the end of the interim study. The initial study includes a booster vaccine to be given at a later date to help boost immunity – this might be key to proving the value of this vaccine. I will wait to celebrate until after I see the results of this part of the full study.

But shouldn’t we celebrate all new vaccines? I think this might be an example of where the public health community is so trained to believe in the power of vaccines that there is little questioning of whether a new vaccine is better than none. In this particular case, I am not so sure. By the way, I blame Bill Foege’s excellent book “House on Fire” for making such a skeptic when it comes to traditional public health dogma and vaccination.

I’ve seen two interesting papers in the past year that look at the use of intermittent preventive treatment of children that showed incredibly high levels of protection (you can read more about them here on the topnamen malaria blog) in areas of high disease transmission. Will this vaccine be better than that option? Those drugs are available now.

When I travel I take a prophylactic drug to prevent malaria, would this vaccine be a better option for me than what I currently do? I would likely need 3-4 shots of the vaccine, which seems like a pain compared to my one pill a day. Is this why GSK has been so quick to say it will not try to capture profits from this new product?

I have heard talk recently of using more powerful drugs like ACTs, which are also known to block transmission, in a mass drug administration type way to dramatically reduce community levels of the disease. Would this not be worth trying?

Is this the best vaccine in the pipeline or just the furthest along? If the world commits itself to this particular vaccine would there be a risk of slowing the speed of development of a better vaccine? Why was there so little discussion of this paper published last week in Science that shows promising results from a live attenuated vaccine in preventing infection.

Would a vaccine work better in areas of low of high transmission?

To be clear, this is an exciting scientific discovery. Kudos to the authors of this paper and to the countless others who have been involved with this venture for decades for their excellent scientific work. But in my mind there are still a lot of big unanswered questions before decisions can and should be made about using this vaccine in the real world.

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