The R21/Matrix-M malaria vaccine showed 71%-80% efficacy in preventing cases of malaria in a randomised controlled phase 2 trial published at the end of last year. A phase 3 trial is ongoing.

67 (51%) of 132 children who received R21/Matrix-M with low-dose adjuvant, 54 (39%) of 137 children who received R21/Matrix-M with high-dose adjuvant, and 121 (86%) of 140 children who received the rabies vaccine developed clinical malaria by 12 months

(the rabies vaccine was the control)

The next best thing is the RTS,S/AS01 vaccine, which WHO started rolling out in some pilot programs in 2016 after trials showed its reduced hospital admissions from severe malaria by around 30%, less impressive than R21/Matrix-M.

A few days ago, Ghana's food and drugs administration announced that they've approved the R21/Matrix-M for children aged 5 months to 36 months. It seems like there will be more steps before the vaccines actually start rolling out (they might need to wait for WHO approval and/or the results of the phase 3 trial). In any case, very exciting news.

I found out about this because it is on the In the news section of the front page of Wikipedia.

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Shoutout to the 130-ish people in the UK who volunteered to be infected with malaria in two separate studies at various stages of the R21 development process! Those studies helped identify Matrix-M as the ideal adjuvant, and also provided insight into the optimal dose/vaccination schedule.

I would not be surprised if this small cohort of volunteers accelerated the pace of getting to this result by a year or more. I'm not going to take a chance on plugging in numbers, but that's a lot of lives saved per volunteer. While most of the badass points/moral credit goes to the people who received the jab, we should also feel proud of the people who were lined up behind them ready to endure the same.

Assuming the genuine willingness of volunteers who ended up not being selected, I do not see a differing level of moral praiseworthiness based on the fortune/misfortune of not having the opportunity to be a part of the study.

I agree with this! People get filtered out of the studies for reasons completely beyond their control, even if they really want to join. You just can't help it if your white blood cell count is a tad too low or you have a slight fever the day of study admission. 

I think it's fantastic that countries are getting ahead of the game in welcoming vaccines like this. I would have thought that post-covid we would be better at fast tracking a vaccine like this but it still seems to be taking 2-3x as long as covid vaccines to get to market! Every day of delay = lives lost. Safety is important but think of the counterfactual...

A 70-80% reduction in cases is more effective than many people (including Bill Gates) hoped for and could be a complete game changer, unlike the current vaccine which prevents 30-50%. With 3 out of 4 childhood malaria cases prevented, we would not only see the obvious improvements in malaria mortality, but also a wide array of benefits such as 

- improved energy levels and concentration in children from reduced anemia
- reduced stunting 
- Women with more time to work in agriculture and other business rather than caring for sick kids, 
- More income due to less money spent on healthcare.
- Healthcare system less overwhelmed

And more. Looking forward to it reaching Uganda soon!

Likewise Nigeria:

I'm confused — would someone mind explaining to me how the quoted numbers show 71-80% efficacy?

(Sorry I'm probably being mathematically illiterate here, but if it's a problem I have, maybe others will too!)

(I'm straight up guessing, and would be keen for an answer from someone familiar with this kind of study)

This also confused me. Skimming the study, I think they're calculating efficacy from something like how long it takes people to get malaria after the booster, which makes sense because you can get it more than once. Simplifying a lot (and still guessing), I think this means that if e.g. on average people get malaria once a week, and you reduce it to once every 10 weeks, you could say this has a 90% efficacy, even though if you looked at how many people in each group got it across a year, it would just be 'everyone' in both groups.

This graph seems to back this up:

They're using 1 minus the hazard ratio, the reduction in the proportion of not yet infected people who are infected at any given time. That is, an 80% efficacy would would that if x% of unvaccinated and as yet uninfected people were infected at some time then (1-0.8)x% of vaccinated and as yet uninfected people would be.

The advantage here is that the proportion of people infected would (unless your vaccine is perfect) eventually go to 100% in both groups, so how long you follow them up for will matter a lot.

Nice, that helped clear this up for me!

I think there is a typo here:

(1-0.8)% of vaccinated and as yet uninfected people would be.

Should say:

(1-0.8)*x% of vaccinated and as yet uninfected people would be.


(else I'm still confused, heh.)

Yes, thank you for the correction

Wow! How exciting. Thanks for the update!

Cautiously optimistic here. It should be noted that since the Phase 2 trial showed efficacy dependent on the amount of Matrix M adjuvant used, the adjuvant providing company, Novavax will need to execute better with its manufacturing partners than it has shown it is capable of. Though this company has historically conducted many clinical trials, it has dropped the ball on execution. It failed a phase 3 RSV trial due to arguably unfit trial endpoints and despite being awarded $1.6 B in Operation Warp Speed money for its COVID vaccine, has drastically underperformed in delivering to all markets, including its committed doses to COVAX due to manufacturing slowness/lack of regulatory capture in the US (I'd say only partly their fault here given FDA slow walking them) and deficiencies in licensing and manufacturing expertise (even when working with Serum Institute of India). They started to cancel manufacturing subcontracts, triggering reneg payment settlement clauses (i.e. $185M to Fujifilm Diosynth, GAVI pulling out of a $700M covid vaccine deal due to failure to deliver in time), and in cases where trials were effective such as its flu candidate which passed phase 3 before the pandemic, their vaccine still has not reached patients commercially (Nanoflu, which showed cross-reactive polyfunctional CD4+ T-cell responses and outperformed Sanofi’s quadrivalent Fluzone in a head to head trial).

Been following Novavax since they're in my backyard in the DC metro area and knew people in their COVID vaccine trial (protein subunit, even slightly outperformed Moderna/Pfizer in some efficacy and side effects metrics.... But very few people ended up getting it compared to Moderna/Pfizer due to lateness to market). Stock went from highs ~$250/share during COVID to now ~$8 arguably due to mismanagement (CEO finally recently stepped down). Would be a pity if the company continues its pattern of misfiring here; hope it doesn't fold, and hopefully if they're just providing matrix M they don't end up being the bottleneck in full manufacturing. Case study in better management/Institutional decision making as an EA cause area in my opinion.

Seems like working at Novavax to improve their implementation could be a super high-value career choice!

Makes me think that a list of "companies that are underrated and critical in important supply chains" could be quite a useful resource for people brainstorming career options.

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