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Understanding the thought process behind mixing vaccines

We are in the midst of the most extensive vaccination campaign known to humanity worldwide. Thanks to vaccines, we can now reduce the worldwide mortality rate from this deadly virus. Traditionally, we need two doses of the same vaccine to induce the optimum amount of antibodies and protection against a disease.

The first dose is known as priming, an introduction of a foreign antigen to our immune system. The second dose (known as a booster) administered after an interval creates an immunologic memory against that particular antigen. The vaccine mix-and-match came into play and gained traction with the recently released data showing high efficacy and protection against various strains of the SARS COV-2 virus.

The Oxford Vaccine Group's Com-Cov (Comparing Covid-19 Vaccine Schedule Combinations) vaccine trial uses different combinations of approved Covid-19 vaccines for the first and second immunisation shots. The study is led by chief investigator Associate Professor Matthew Snape and is being delivered by a network of trial sites across the United Kingdom.

The Com-Cov study involved 850 volunteers aged 50 and above. The AstraZeneca and Pfizer vaccines were given four weeks apart and induced higher antibodies and T-cell responses than Pfizer followed by AstraZeneca.

Both of these mixes induced higher antibodies than two doses of AstraZeneca and gave better protection. The highest antibody response was seen after two doses of Pfizer, and the highest T-cell response was from AstraZeneca followed by Pfizer. Volunteers had a relatively tolerable reactogenicity profile (side effects).

Mixing the two types of vaccines may give the immune system multiple ways to recognise a pathogen. Different vaccines present the same information differently and may awaken other parts of the immune system or sharpen the immune response. This strategy could also make immunity last longer.

Another study by German researchers showed that administering the first dose with AstraZeneca followed by Pfizer elicits higher anti-spike titres and more neutralising activity against the Alpha, Gamma and Beta variants. Mixing Covid-19 vaccines is emerging as an excellent way to get people the protection they need when faced with safety concerns and unpredictable supplies.

Multiple studies now back up the idea that mixing the Oxford- AstraZeneca vaccine and the Pfizer–BioNTech vaccine triggers an immune response similar to — or even stronger than — two doses of either vaccine. Results announced last Monday by a UK group suggest that the combination sometimes outperforms two shots of the same vaccine.

The Ebola vaccine developed by Johnson & Johnson is an example of a mixed-dose approach. If the Covid-19 vaccine rollout applies the mix-and-match technique, it can significantly increase flexibility. Having a flexible immunisation programme allows us to vaccinate more people in the face of global supply constraints.

If there's a shortage of one vaccine, instead of halting the entire programme to wait for supply, the programme can continue with a different vaccine, regardless of which one has been given as a first dose.

Suppose one vaccine is less effective than another against a certain variant. In that case, mix-and-match schedules could ensure people who have already received one dose of a vaccine with lower effectiveness get a booster with a vaccine that's more effective against the variant.

Mixing the vaccines can help to prevent immunity against adenoviral-based vaccines. How? When it comes to Covid-19 vaccines, Russia's Sputnik V, Johnson & Johnson (J&J), CanSino Biologics and AstraZeneca products use a modified adenovirus to express the coronavirus spike protein that the immune system activates against. It is "replication-deficient", so it can't copy itself in the body once injected and give us a cold.

The immune system can develop a response against the adenovirus platform. Sputnik V uses a different adenovirus in each shot to get around this possible risk. If a third dose is needed, which is possible if vaccines are updated to address variants — a viral vector vaccine would not be optimal.

From this perspective, it makes sense to change platforms to mRNA or protein-based, like Novavax.

CanSino and J&J vaccines are easier to store and don't require people to return at a set time for the second jab — something that's hard to guarantee, especially in developing countries. One vaccine, single visit and cheaper logistics. It has all those advantages.

The J&J coronavirus vaccine is effective against the highly contagious Delta variant, even eight months after vaccination, the company reported on Thursday. This should reassure the 11 million Americans who have gotten the shot.

The vaccine showed a small drop in potency against the variant, compared with its effectiveness against the original virus, the company said. But the vaccine was more effective against the Delta variant than the Beta variant, first identified in South Africa — the pattern also seen with mRNA vaccines. Antibodies stimulated by the vaccine grow in strength over time.

The writer is a molecular virologist and senior lecturer at Monash University Malaysia, specialising in virus-host crosstalks and its implications on viral pathogenesis


The views expressed in this article are the author's own and do not necessarily reflect those of the New Straits Times

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