Coronavirus Vaccines: Two Different Doses May Give You Better Immunity


Most Australians will receive either the Pfizer vaccine or the AstraZeneca vaccine, even despite a change in advice due to rare side effects from blood clotting.

Now a new complication is emerging: what if the best option, to achieve the greatest immunological response, was to take both vaccines, one dose of each?

This is not a new idea, but most of the research has been on animals or preclinical trials (using human cells) with potential universal HIV or flu vaccines.

Often, but not always, researchers have found that the immune response is stronger when two different types of vaccines are used.

However, full-fledged human clinical trials of this strategy – known as heterologous prime-boost – has so far been too expensive and difficult.

But in the era of COVID-19, well-funded research opportunities abound.

And, as a University of Melbourne researcher put it TUSEN, with vaccines coming and going out of favor, we can expect to see a large number of people being given two different vaccines, as logistics will demand it.

How did this possibility arise?

In a bid to keep their vaccination program running, British health authorities in January issued an order that seemed to be a sign of desperation: if people were to receive their second vaccine and if their initial vaccine was not available, they were to receive it. regardless of the type of COVID-19 vaccine available.

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So if you had initially received the AstraZeneca vaccine, but could not access AstraZeneca for the booster, you will receive the Pfizer vaccine instead.

In the UK, France and Europe, people receive both Pfizer and AstraZeneca vaccines.

There was no evidence that this strategy would work with COVID-19 vaccines or that it would be safe.

But a month later, the University of Oxford began the world’s first clinical trial with volunteers to see how well mixing and pairing COVID vaccines would work.

Scientists around the world are eagerly awaiting the results to arrive – even though European regulators are already pushing ahead with plans to adopt the strategy.

Last week, French health regulators responded to AstraZeneca’s blood clotting problem by recommending that people under the age of 55 who received their first dose of AstraZeneca receive Pfizer or Moderna for their second injection.

Germany is taking the same path for people under the age of 60 who have received a single photo from the AstraZeneca.

It’s unclear what kind of useful data is being collected from these French and German experiences – probably not much, and unlikely without the rigor of a clinical trial structure.

How could this work?

Dr Adam Wheatley is a senior researcher specializing in microbiology and immunology at the University of Melbourne.

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He leads a research team studying particular mechanisms to generate broad and long-lasting antibody-based protection against infectious viral diseases.

Dr Wheatley said that because COVID-19 vaccination is “a rapidly changing space, with vaccines coming in and going out of favor and safety signals appearing, I think there will be a large number of people who [are] eventually given two different injections simply on the basis of different logistics, or by changing the vaccine advice ”.

He said that in the real world of pandemic conditions: “There is the idea that you get yourself everything you can and vaccinate as many people as you can. And then you get all you can for the second booster shot.

He said this was not motivated by any scientific idea as to what the optimal approach would be, but previous research suggests that the heterologous prime-boost may offer better immunity.

Dr Wheatley said a lot of research has come from efforts to develop HIV and universal influenza vaccines.

He said: “A lot of experimental work has been done in animal models and up to preclinical trials which have established that when you change the modality of the vaccine between the first and the boost, you often, but not always, get. a greater elicitation of an immune response than you would if you gave just two injections of the same single agent. “

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In a simplistic sense, is this a bit like taking the immune system by surprise?

“It’s kind of like that,” he said.

“There are various theories as to why this might work. One of them is that you are using two different pathways to tickle the immune response. “

So when you deliver the first vaccine (such as Pfizer based on mRNA technology) it may “alarm parts of the immune system”.

If you follow up with AstraZeneca (a so called adenovirus vaccine vector) it might stimulate slightly different arms of the immune system.

“The idea is that by mixing and matching two different vaccine platforms, you expand the range of immune cells that are recruited into this vaccine response and end up with a more potent response to this vaccine,” said Dr Wheatley.

Another reason for using two different types of vaccines, he said, is that the body develops an immune response against the vaccine itself – and a second dose will tend to be less effective.


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