Why Delaying AstraZeneca Dose 2 INCREASES Efficacy?

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Many people have asked me to explain WHY delaying the second dose of the AstraZeneca vaccine INCREASES its efficacy.

It sure is a very odd phenomenon, when you think about it!

 

Delaying AstraZeneca Dose 2 INCREASES Efficacy

Let me start by confirming that yes, delaying the second dose of the AstraZeneca vaccine INCREASES its efficacy.

The AstraZeneca vaccine was originally designed with a 21-day interval between Dose 1 and Dose 2.

However, this Lancet study showed that the AstraZeneca vaccine’s efficacy increased with longer delays between Dose 1 and Dose 2!

I summarised their findings into this table, to show you how the AstraZeneca vaccine’s efficacy changes with the dose interval.

Dose 1 to Dose 2
Interval
EfficacyDifferenceEfficacy Range
< 6 Weeks55.1%Baseline33.0% to 69.9%
6 – 8 Weeks59.9%+8.7%32.0% to 76.4%
9 – 11 Weeks63.7%+15.6%28.0% to 81.7%
≥ 12 Weeks81.3%+47.5%60.3% to 91.2%

Doubling the dose interval from the standard 3-4 weeks increased its efficacy by 8.7% – a small but significant improvement.

The greatest benefits came from even longer dose intervals :

  • 9 to 11 week dose interval : + 15.6% increase in efficacy
  • 12 week dose interval or longer : +47.5% increase in efficacy!

That’s why health authorities changed their guidelines to give the second dose of the AstraZeneca vaccine 12 weeks later, instead of 3 weeks.

 

Why Delaying AstraZeneca Dose 2 INCREASES Efficacy?

Many people have asked me to explain WHY delaying the second dose of the AstraZeneca vaccine INCREASES its efficacy.

When you think about it – it sure is a peculiar, and rather illogical, phenomenon, isn’t it?

Frankly speaking, no one knows WHY this is the case, and it will be some time before anyone can prove the mechanism of action behind this phenomenon.

Therefore, I can only offer my hypothesis based on what I read in the many AstraZeneca studies.

Why Shorter AstraZeneca Dose Interval Reduces Efficacy?

Vaccines Are Training Camps

First, we must understand that COVID-19 vaccines are just training camps that teach our own immune system how to identify the SARS-CoV-2 virus.

COVID-19 vaccines basically show our immune system what the SARS-CoV-2 virus (or a key part of it, like the famous spike protein) looks like.

Our immune system identifies it as a “foreign enemy” and learns how to make antibodies against it. These antibodies provide some protection against a real SARS-CoV-2 virus attack.

And when a real attack does come, our immune system, which now recognises SARS-CoV-2, can quickly produce even more antibodies to defeat the coronavirus.

Did Salk Institute Prove Covid-19 Vaccines Cause Blood Clots?

First Dose Offers 3 Months Protection?

The same Lancet study also showed that the first dose of the AstraZeneca vaccine consistently offers good protection for the first 3 months.

Basically, our immune system remembers the lesson taught by the “first class” (first dose) very well for 3 months.

Time After 1 DoseEfficacyEfficacy Range
22 to 30 days76.7%47.0% to 89.8%
31 to 60 days72.8%32.9% to 89.0%
22 to 90 days76.0%59.3% to 85.9%
61 to 90 days78.3%36.4% to 92.6%
91 to 120 days31.6%-141.8% to 80.7%

So here is my hypothesis.

Since our immune system remembers the lesson from the first dose so well in the first 3 months, it does not benefit much from an early refresher course – the second dose.

A refresher course is important – it reminds our immune system that COVID-19 is a recurrent threat that must be taken seriously, and kicks our memory B-cells out of hibernation.

But as you may recall from your college days – a refresher class a month after the class really isn’t as effective as a refresher class just before the term exam!

Refresher class

And that, I believe, is possibly the reason why a longer dose interval increases the AstraZeneca vaccine’s efficacy – an actual “refresher class” is far more useful to our immune system than a “repeat class”.

A new preprint paper in the Lancet appears to back-up the evidence that longer dose intervals improve the AstraZeneca vaccine’s efficacy.

It showed that longer dose intervals like 15-25 weeks and even 44-45 weeks were associated with higher antibody response when Dose 2 is administered!

45 Week AstraZeneca efficacy preprint chart

 

Should We Keep Delaying AstraZeneca Dose 2 For More Efficacy?

Now, it is true that the evidence shows that delaying the second dose of AstraZeneca improves its efficacy.

However, and this is very important, we have to balance that against the RISK of getting infected by COVID-19 while we delay taking Dose 2.

The Delta variant, for example, is proving to be particularly problematic. A single dose of AstraZeneca vaccine does not provide good protection against it.

COVID-19
Variant
Symptomatic
COVID-19
Hospitalisation
1 Dose2 Doses1 Dose2 Doses
Alpha (UK)50%66%76%86%
Delta (India)33%60%71%92%

Therefore, we cannot keep delaying the second dose of AstraZeneca in hopes of getting better and better efficacy.

The increased efficacy from waiting will be pointless if you get infected before getting that second dose!

That is why many health authorities are now shortening, or planning to shorten, the dose interval for AstraZeneca – sacrificing some efficacy to gain more protection against the Delta variant earlier.

As I detailed in my earlier article – AstraZeneca Vaccine : Accept Or Delay 9 Week Dose Interval? – there really are no simple answers…

 

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