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Infectious Diseases

Great Malaria Vaccine News

Excellent news today: we have word of the most effective malaria vaccine yet discovered. A year-long trial in Burkina Faso has shown 77% efficacy, which is by far the record, and which opens the way to potentially relieving a nearly incalculable burden of disease and human suffering.

This is a collaboration between the University of Oxford (Jenner Institute et al.), the KEMRI Wellcome Trust in Kenya, the London School of Hygiene and Tropical Medicine, Novavax, the Serum Institute of India, and especially the Institut de Recherche en Sciences de la Santé in Nanoro, Burkina Faso. Let’s talk about Nanoro a bit. It’s in central Burkina Faso, west/northwest of the capital Ouagadougou. Here are some shots of city, town, and rural village life in this part of the country (panel B is in Nanoro itself). The town is in a climate zone with a classic tropical pattern: hardly any rain at all in the hot season (December, January, February) and then a monsoon season in the summer and fall. That brings on masses of mosquitos, and malaria is an absolute scourge.

Past studies from the Nanoro health sciences institute make this terrifyingly clear. Here’s one where they looked a cohort of 734 infants born in the area for the first year of their lives. It’s thought that children of this age have some malaria protection due to antibodies passed on from their mothers, but as the paper says, in areas of high transmission this can be overwhelmed. In those 734 infants, they recorded 717 clinical incidents of malaria infection, with the incidence rate strongly increasing as their first year went on and the great majority of these occurring in the rainy season. This 2010-2014 study from Nanoro shows the strong correlation of local malaria cases with rainfall and temperature (with a few weeks lag, as expected), and also with socioeconomic status (in exactly the direction you’re thinking). This is the clearly the sort of region where real-world tests of a malaria vaccine need to be carried out.

This new vaccine (R21) uses a circumsporozoite protein (CSP) antigen – that’s a highly conserved protein of the parasite, involved in several functions as the parasite makes the move from mosquito to human and into different human tissues such as the salivary glands. This has been a vaccine ingredient before, such as in the RTS,S vaccine (the first one ever licensed), but R21 has a much higher proportion of CSP assembled into a virus-like particle. It also uses the exact same adjuvant from Novavax (Matrix-M) that they are using in their coronavirus vaccine – you can’t keep a good adjuvant down, and this Chilean-soapbark-based one seems to really kick the immune system up under all circumstances.

The team previously run an “age-de-escalation” trial in Kenya, showing that the vaccine seemed safe as you moved down to children and infants. That led to this trial, in 450 children aged 5 to 17 months in the Nanoro area, in three groups: 150 children with 5 micrograms vaccine and 25 micrograms adjuvant, a second 150 at 5/50, and a third getting rabies vaccine as a control. Three shots were given in the May-August period, largely before the yearly transmission period, and everyone got a booster shot one year later. The participants, their families, and the local study team were all blinded to the group assignments. Antibodies were measured at several intervals over the next year, and malaria cases were of course monitored.

The higher-adjuvant cohort showed 77% vaccine efficacy, and the lower-adjuvant one showed 74% with (as you’d expect) overlapping confidence intervals. The first group had significantly higher antibody levels, though, and they’re currently doing an additional year of follow-up to see how long the protection lasts and if these doses differentiate themselves. The antibody levels at the one-year mark in both groups were significantly higher than with the RTS,S vaccine, and in particular, antibodies against the repeat section in the middle of the circumsporozite protein seemed to correlate strongly with protection. No safety problems so far.

The team is now planning a larger Phase III at five different African site, with varying seasonality and malaria loads. The Serum Institute is manufacturing the vaccine itself, and they say that they have a large-scale production route. The Novavax adjuvant is currently in a bit shorter supply due to the coronavirus pandemic, but it’s still easier to manufacture and scale than the one used in the RTS,S vaccine. And while the dosing schedule used in this trial is a demanding one, I hope that the Phase III will help to establish the best balance between the logistics of dosing and malaria protection. Overall, this is definitely the best malaria vaccine candidate the world has yet seen, and that is unequivocal good news. Congratulations and thanks to the widespread group of researchers who have made this possible – and especially, thanks to 450 infants and toddlers in central Burkina Faso and to their parents. You have done the world a great service.

59 comments on “Great Malaria Vaccine News”

  1. Alex says:

    I wonder if this works against falciparum malaria or vivax, ovale, and the other types as well. In Southeast Asia there are many strains of malaria that are fully resistant to ACT, which would make this vaccine a true life saver there.

    1. Derek Lowe says:

      I think that Burkina Faso is 100% falciparum. And I see from the literature that people have worked on the CSPs from vivax, etc., as well as with the falciparum one used in this trial, so maybe the same approach can work!

      1. Mimi Emig says:

        The paper states this vaccine targets P. falciparum. Since this is the most deadly form of malaria, it makes sense to go after this first.

        1. Clem says:

          that really depends! I would say it is just as important to consider ones that are more prevalent in a wider area and to consider the absolute number of people who die. If one has a death rate of 30% and the second one 15% but the second one kills 10X as many people in a year that would be the one to go after.

          1. Nesprin says:

            Falciparum is known to be both more widespread and more deadly, so making inroads on this strain will make a huge difference to the largest swath of people. Other strains are endemic in different regions with different mosquito burdens, such as southeast asia.

          2. confused says:

            Isn’t the difference in mortality much larger than 2x though? (At least vs. the Latin American types… I have no idea what the Asian strains are like…)

  2. Sulphonamide says:

    A stunning effort indeed – amazing how suddenly something as immovable and insoluble as malaria can suddenly (if it all works out of course – but even so this is a gargantuan improvement on anything we’ve seen before) be seismically shifted by investment and the coming together of the required technologies (hasn’t even required mRNA vaccines). But presumably there are enough non-human hosts that malaria will always be waiting in the wings ready to come back at the slightest dip in investment, break in supplies or social upheaval? Still wonder if gene drives for controlling the mosquito vectors might not be a more economical way to eradicate (or as near as) the disease, if we can sort out the environmental ethics of it. Either way, there goes a much loved final year dissertation topic – hopefully its TB equivalent will also be nearing the end of its shelf life.

  3. Eric says:

    Hmmmm, maybe should have bought that Novavax stock after all.

  4. Anon says:

    Any concerns about drug resistance??

    1. Mister B. says:

      I don’t know how “vaccine resistance” would work but this was my second thoughts after a big loud, YUUUUUP !

      That’s super good news Derek, thank you very for this !

      1. Anon says:

        I don’t know the difference between this and antimalarials either. I was just curious. Hopefully someone will explain here.

        1. metaphysician says:

          They key difference, from my layman’s perspective, is that antimalaria drugs are basically poisons that have to target the parasite. It can evolve resistance via various means, like pumping them back out.

          A vaccine targets the immune system, and the immune system is scary powerful from a microorganism perspective. The parasite would either have to evolve defenses against the many vectors of attack, or else avoid drawing notice in the first place. That is presumably why this vaccine targets a highly conserved protein: its something malaria *can’t* change to evade detection, not without crippling the organism. If the immune system twigs to that protein, then curtains.

          ( Simple becoming invulnerable to the various forms of immune attack is, as i understand it, close to impossible. The immune system is *really* good at killing things in a variety of ways. Once it decides that you are an invader, it *will* kill you, even if it also kills the host. )

          1. Microbiologist says:

            Another difference between antimicrobials and vaccines causing resistance is the population size they generally act on. Antimicrobials are given in response to an infection when the microbial population is large and may contain enough genetic diversity to find a resistant mutant.

            Vaccines act before infection and therefore only need to stop a much smaller, and likely less diverse, population of microbes.

          2. RandomStranger says:

            HIV begs to differ.

          3. metaphysician says:

            HIV is a very special case, and is absolutely not invulnerable to the immune system. It is instead evolved to survive by hiding, essentially, and causing slow cumulative harm to the immune system in each successive resurgence. There is a reason AIDS takes so long to manifest, it needs many cycles of propagation and suppression before the immune system is weak enough for it to actually thrive.

            Essentially, HIV is not an indestructible tank. Its a guerilla fighter that hides away a couple new guerrillas so that *when* the army wipes out all the rebels, these hidden guerrillas can come out and recruit later.

        2. A Nonny Mouse says:

          Lots of new antimalarial drugs being developed by MMV. Sorted a few processes out for them in the past. A couple moving forward..

      2. Not-an-epidemiologist says:

        I don’t know how “vaccine resistance” would work but this was my second thoughts after a big loud, YUUUUUP !

        I’ve linked to this review article before, but in general — vaccine resistance is rare (much less common than drug resistance), and even when it does arise there is generally still some protection offered by vaccines. Influenza is very much the exception, not the rule.

        1. confused says:

          Cool, thanks for the link. I knew that vaccine resistance wasn’t usually a thing that has happened historically (with the weird exception of flu, yeah) but didn’t know why.

  5. CET says:

    I remember when I was somewhat younger, I wanted to go into drug development because I wanted to be part of something that would actually make a difference to people.

    It is amazing to see this kind of achievement. In terms of lives saved, suffering averted, and human potential unlocked…I can’t think of anything this big since….polio? The discovery of antibiotics?

  6. Terrific news, and good on the institutes participating such as KEMRI-Wellcome.

    Been needing to hear good news in health lately, especially related to Africa and emerging markets.

  7. J says:

    ‘Malaria vaccine hailed as potential breakthrough’

  8. ScientistSailor says:

    Will this be good enough to eradicate it?

    1. sgcox says:

      Yes, but only after we inoculate all the live stock and ideally wild animals in Africa, most of America and South Asia. I heard lions have a particularly strong antivax sentiments.

      1. notaparasitologist says:

        Less of a problem than you might think, because P.falciparum is almost exclusive to primates.

        1. ScientistSailor says:

          Yes. and only one species of mosquito spreads it to humans…

          1. Sulphonamide says:

            One genus I think? Lots of different Anopheles can transmit it to humans and they thrive in all sorts of different environments (usually neglected and damaged ones…) or did you mean that only one species transmits from non-human primates to humans? That might be a crucial gap to exploit if it were the case.

    2. Barry says:

      Eradication is a lofty goal. We managed it for smallpox, which had no wild reservoir (non-human host) but also for rinderpest, which had non-human hosts. Eradication of Malaria remains unlikely. But if it were merely as well controlled around the world as e.g. tetanus is in the U.S., that would be great.

  9. lapsed chemist says:

    What a great start to the weekend! This is a milestone achievement – well done to all the scientists involved – past and present!

  10. dearieme says:

    President Micron has announced that this jab is from Oxford and is therefore quasi-ineffective.

    1. Marko says:

      He has just now changed his mind.

    2. WST says:

      I tried to trace this statement by president Macron and could not find it.
      Macron is 43 and declared that he will wait his turn, he had covid in December.
      Only article suggesting Macron is against AZ was from Daily Mail, quoting a journalist from Russia Today. RT and Sputnik journalists are not invited to presidents briefings and are not regarded by the official France as news agencies but rather a Russian propaganda outlet, so reports of what Macron said by an RT journalist is not a first hand account.
      Right now Macron has initiated large scale communication effort in support for AZ and J&J vaccination.

      In other words, yet another episode of Russian destabilisation campaign against AstraZeneca.

      (AZ and Sputnik combined clinical trial that was supposed to start 30/3 is not recruiting yet, most likely will never do)

      1. A Nonny Mouse says:

        January 29, 2021 4:52 pm

        PARIS — French President Emmanual Macron said Friday the AstraZeneca coronavirus vaccine appeared to be “quasi-ineffective” on people older than 65 — just hours before the EU’s drugs regulator approved it for use on all adults.

        “The real problem on AstraZeneca is that it doesn’t work the way we were expecting it to,” Macron told a group of reporters, including POLITICO, in Paris. “We’re waiting for the EMA [European Medicines Agency] results, but today everything points to thinking it is quasi-ineffective on people older than 65, some say those 60 years or older.”

        1. WST says:

          The date…. it was just after the false claim in “Handelsblatt and Bild” that AZ is 8% effective in elderly. Macron has overacted, no question, but so did quite few EU politicians. This controversy did not took more then a week ebb out.

          It is misleading to use this quote of Macron today without this context.

          Feb 25, 2021, Reuters quotes Macron:
          ““In view of the latest scientific studies, the efficacy of the AstraZeneca vaccine has been proven,” Macron told reporters after a virtual European Union summit. “My turn will come, but I’ve got time. If that’s the vaccine that’s offered to me, I will take it, of course.”

          1. Marko says:

            Wait, I thought it was all Russian disinfo, with no basis in fact ?

            Macron jumped the gun, so mocking him for it is fair game, as it would be for anyone else who made such a careless and damaging blunder.

          2. WST says:

            …and you were right !
            1. Macron never got vaccinated
            2. Macron did not complain about efficiency of the his hypothetical jab

            Two false statement in one sentence completely out of the thread context, bit too much for the regular boneheads.-))

          3. Marko says:

            This is the start of the thread:

            “President Micron has announced that this jab [the malaria vaccine] is from Oxford and is therefore quasi-ineffective.”

            This was clearly an appropriately sarcastic and mocking shot at Macron, referring to his earlier blunder regarding the AZ vaccine, which you recognized as such. You then claimed you could find no evidence of that earlier statement and that it was all part of a Russian disinfo campaign. Now that Macron’s earlier statement has been substantiated, rather than simply manning-up and admitting your error, you’re dissembling. Pretty lame.

          4. WST says:

            I”m sorry, I thought the thread was about malaria vaccine.

      2. Jonas says:

        I would not just blame the Russians. There has a lot of dirty water thrown at the Oxford and AstraZeneca effort from people all over, even Australia. I often wondered if they have vested interests in the likes of Pfizer -or just hated the idea of not for profit products that may press down profits across the industry generally. We may never know.

      3. A Nonny Mouse says:

        Incorrect (again)

        Gamaleya and AstraZeneca have registered a pair of clinical trials in which volunteers will receive a dose of AstraZeneca’s vaccine and another of Sputnik V.

        One trial in Azerbaijan is underway, and a second in Russia is still under review by the country’s ministry of health.

        1. WST says:

          re: Nonny Mouse

          Timing is everything, Russians started disinformation campaign last summer, as described by The Times and EU’s information disinformation site.

          Then the attacks stopped when the cooperation you mentioned was announced. There is very little information about these trials although the 100 subject Azerbaijan trials should have started recruiting end of March.

  11. BF Ansari says:

    yes, this could be great news.

  12. Jonas says:

    So reading this article and associated press media pieces, it seems that this is not the discovery of hitherto elusive effective vaccine, but also assured accessible development?

    If so, this is massive!
    Since when are vaccine scientists thinking ahead to practical issues such as mass manufacturing and accessibility AND actually incorporating this into a plan?

  13. Michael says:

    Is there any indication of whether this vaccine will, in addition to preventing initial cases of malaria, prevent relapses in people who have previously been infected and are prone to them?

    1. Christian Weisgerber says:

      This vaccine candidate is against P. falciparum malaria, which is non-relapsing.

  14. marp says:

    This is fantastic! I had no idea vaccines could be discovered!
    All the ones I know of were invented by humans. Was it hiding under a rock at the bottom of the ocean, maybe?

    1. sgcox says:

      Yes, this is a good one !
      When I run HTS against enzyme #15 and find a good hit, I discovered it, not invented it, right ?
      Then, when chemist makes 100 analogues and stumbles on say meta-chlorine which jumps the potency, did she/he invented it or discovered ?
      Of course, it will be claimed in JMC paper it was rationally designed. But why did you make other 100 inactive compounds prior to the breakthrough if this was indeed the case ? There will as usual the post-hock structural based design analysis as well, once after many heroic efforts, biologists get the target finally crystallised with that all important compound, etc.
      So what is discovered and what is invented in drug discovery ?
      Same with vaccines – hundreds were invented and only few were discovered to be effective.
      Now, discuss 🙂

      1. Druid says:

        Inventions have to be invented to be patentable, apart from all the discoveries (eg pre-existing DNA or amino acid sequences) that the patent office lets through for some reason no-one understands. But your assays are purposely-designed tests for the action designed into the invented compound, unless your assays are random. Even screening assays were designed for a purpose; that’s why assays are intellectual property. On the other hand, anything from a library run through a set of screening assays is a discovery (as it already exists) and therefore not patentable (except that in some countries the chemistry used to make the compound is patentable). In my opinion. See you in court where someone who studied law instead of chemistry can decide.

    2. Jonas says:

      The vaccine was designed in a deliberate way, so was invented! But you have run a trial to “discover” how effective it is -of at all.
      This news comes from an arito le about the trial.

  15. JasonP says:

    Does this mean that the only use left for Hydroxychloroquine is early treatment of asymptomatic COVID-19??? 😉

    1. Morten says:

      Well done, sir. Well done indeed. 😀

    2. eub says:

      Zinc supplements may be poorly absorbed, and this can be boosted by hydroxycloroquine?

    3. A Nonny Mouse says:

      Lupus remains

  16. APAJ says:

    Ah! True dedication to science:
    “[…] 450 children aged 5 to 17 months […] . The participants […] were all blinded to the group assignments.”

  17. Smokerr says:

    I think discovery is the wrong world.

    Development would be accurate term I think. Fantastic news if it holds up, one of the tragedies is not having been able to break that Malaria cycle.

  18. O.K. says:

    Are there any concerns that using the same viral vector ChAdOx1 in this malaria vaccine and Oxford/AstraZeneca’s COVID-19 vaccine will reduce the efficacy of the second one that is administered? As in, if a significant percentage of the African population is inoculated with Ox/AZ’s COVID-19 vaccine, we might find that this new malaria vaccine doesn’t work as well because their immune systems developed resistance against the ChAdOx1 vector?

    1. sgcox says:

      Malaria vaccine from Oxford is not based on adenovirus.
      It is recombinant protein, same one as discovered(invented) by GSK and active ingredient of approved Mosquirix. Oxford vaccine is much more effective because they improved formulation and used the adjuvant from Novavax. Do not know full details but they should be published, or will be soon.

    2. J says:

      ‘High Efficacy of a Low Dose Candidate Malaria Vaccine, R21 in 1 Adjuvant Matrix-M™, with Seasonal Administration to Children in Burkina Faso
      30 Pages Posted: 20 Apr 2021 ‘

    3. Derek Lowe says:

      It’s not an adenovirus vector – Oxford’s Jenner Institute has a number of different things going on.

      1. O.K. says:

        Oh, I was misinformed. I remember reading a news article saying it was based on the same platform, but that science reporter must have been sloppy. My fault for not doing my own research. Thanks for the correction.

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