Thread by @michaelmina_lab

VACCINES can work!

Another #COVID19 phase 3 vaccine trial reports awesome results. This time, an estimated 94% efficacy

95 COVID19 detected: only 5! in the vaccine group and 90 in the placebo

But like Pfizer results - need to take w caution... WHY?

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investors.modernatx.com/news-releases/…

First, the amazing efficacy from phase 3 at this point for both @moderna_tx and @pfizer vaccines - both mRNA vaccines - is EXCEEDINGLY ENCOURAGING.

These results show that these vaccines are eliciting the correct antibody bases responses to stop symptomatic infection!

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What I am worried about is the time scale of the trials thus far:

The leading vaccines are presenting the spike protein to the human immune system. This makes sense! Immunize against spike and stop virus entry into the cells.

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But that these vaccines are designed specifically around antibody based responses suggest these early phase 3 endpoints - which are detected within a couple of months of getting the vaccine - may be enjoying a major but temporary boost from the early vaccine effects

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When you get an infection or a vaccine, the body makes a HUGE number of temporary antibody secreting cells called plasmablasts.

These are evolutionarily “designed” to infuse a huge and robust antibody response capable of clearing an active infection

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But over the month or so after the infection or vaccine, the plasmablasts have to die off - it is their fate. Over the coming weeks and months so too do the antibodies they produced.

What remains after is usually a much smaller antibody producing cellular subset

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So I am a bit hesitant to jump on board with the >90% efficacy results because the time scale of the phase 3 studies thus far match the time scale of the temporary plasmablast duration and the antibodies they produced...

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So, w these early efficacy results, we may be measuring the effects of an impressive front line army that spins up in response to the vaccine - but then we should be careful not to assume the same efficacy persists to hold that line after most of the troops disappear!

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That all said - what these two vaccines show is they hit the nail on the head to find the right protein to immunize against!

Only time and careful follow up will tell how much the >90% efficacy of the two vaccines holds after the early vaccine responses fade away.

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This is btw generally why we must monitor durability of vaccine responses over time. And why we have to always be careful to interpret efficacy within the parameters of the data we have (here - early months post vaccine)

Also - we don’t know about transmission blocking...

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To learn about the actual benefits long term of the vaccine reaponse - it will take continued post market analysis. The controls will likely get the vaccine - so a new type of vaccine study that is not as well controlled will ensue to measure longer term effects.

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Also - I’m not speaking in black and white terms here. Either way, immunity will likely persist. It’s not binary. B and T cells are produced

At population level, we must wait to see if 94% efficacy to fully block symptomatic disease becomes 90% or if it becomes 50%, or 30%

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And even if it becomes 50% to stop total symptomatic disease, it could remain 90% to stop severe disease. This, like testing and everything else is simply NOT a binary issue and also is NOT a simple issue meant for describing over Twitter....

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