Combination vaccine
Roughly 4.25 million doses of COVID-19 vaccines are now given every day around the world. Amidst the production and logistical challenges, scientists have started human trials in the UK to combine vaccines to test their efficacy. For illustrative purposes only. Image Credit: Gulf News/File

DUBAI: As history's biggest vaccination campaign gets underway, the first trial of a combination COVID-19 vaccine kicked off on Thursday, February 4, 2021. It has one simple aim: get immune response data from several hundred volunteers after they get a combination of two approved vaccines. In so doing, the researchers hope to push the bounds of science.

Vaccinations are getting ramped up, across the world with 108 million doses administered as of Thursday, according to Bloomberg data. But more mutations are also seen (some 4,000 viral mutations of the SARS-CoV-2 had been reported), raising questions about the approved vaccines' efficacy against new strains. Now, at least two trials had been unveiled to combine different vaccines in the hope of eliciting better efficacy against the virus. Here's the lowdown on the vaccine cocktail trials:

What COVID-19 vaccines are being combined?

There are two human trials for combination COVID-19 vaccines. The first will examine the immune responses of an initial dose of Pfizer-BioNTech vaccine, followed by a booster of AstraZeneca shot — as well as vice versa — with intervals of 4 and 12 weeks. This trial kicked off in Britain on Thursday. Another two-shot schedule will conduct clinical trials of the combined AstraZeneca-Sputnik V vaccines. It's expected to kick off soon.

108 million doses against COVID-19
• Roughly 4.25 million doses of COVID-19 vaccines are given every day
• More than 108 million doses have been administered across 67 countries, according to Bloomberg data.

What is the objective of the new combo vaccine trials?

The trial itself will not assess the overall efficacy of the shot combinations. Instead, the researchers will measure antibody and T-cell responses, as well as monitor for any unexpected or adverse side effects, according the UK researchers.

How vaccines Compare
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Scientists say it’s possible that mixing jabs could give even better protection. One of the expected metrics of the trial is the data that would answer the question: Would giving people different COVID-19 vaccines for their first and second doses work as well as the current approach of using the same type of vaccine twice?

This will allow researchers to see if giving people different COVID-19 vaccines for their first and second doses works as well as the current approach — using the same vaccine for both primary and booster shots.

What’s the benefit of having a combination vaccine?

It is hypothesised that the combined shots will provide greater flexibility for vaccine rollout — and help deal with any possible supply disruptions. Under the present protocol, this is permitted but only in extreme cases. The official guidance in most jurisdiction states that anyone already given a vaccine should get the same vaccine for both doses. The US Food and Drug Administration and the UK’s Joint Committee on Vaccination and Immunisation (JCVI) recommend as much. It's only in “very rare circumstances” that different vaccines may be used — and only if one vaccine is available at different times, or it's not known which one was administered for the first dose.

When are the new trial results due?

For the Pfizer-AstraZeneca combo, initial data readout (level of immune responses) are expected around June 2021.

How different are the Pfizer and AstraZeneca vaccines?

The two vaccines were developed using altogether different platforms. The BNT162b2 shot developed by Pfizer came from BioNTech, which uses the messenger RNA technology, a new method. The Oxford/AstraZeneca shot, known as AZD1222 in the UK (Covishied in India), uses the adenovirus viral vector platform, a tried-and-tested technique. The Pfizer vaccine has a prescribed 12-week gap between the first and second shots. The AstraZeneca shots also have a 12-week (84-day) gap between two shots.

Were there any vaccines combined in the past?

Combining jabs is nothing new. The UK’s Vaccine Deployment Minister Nadhim Zahawi said mixing doses is “something that is done historically” with other vaccines such as jabs for hepatitis, polio, measles, mumps and rubella. Another example: the Ebola immunisation programmes also involve mixing different jabs to improve protection.

How many volunteers will participate in the Pfizer-AstraZeneca combo trial?

More than 800 participants are expected to take part. Recruitment started on February 4, 2021.

What’s the science behind using one vaccine as primary and another as booster?

Scientists believe that following the approval of individual vaccines, the cocktail approach against COVID-19 may prove beneficial. In the Pfizer-AstraZeneca combo, scientists want to find out if the vaccine combination would be practical. Vaccine developers in the past have combined several separate shots into one to protect people from infectious or viral diseases with a single jab. For example, the vaccine Pentacel has been approved to innoculate children against diphtheria, tetanus, pertussis, polio, and Hib (Haemophilus influenzae type b). Another is MMRV, a four-in-one shot against measles, mumps, rubella, and varicella.

• Traditionally, in vaccinology, combination of vaccines means taking two or more vaccines that could be given individually and putting them into one shot.

• They give the same protection as they do from individual vaccines given separately — but with fewer shots.

• One example of a combination vaccine is DTP vaccine, a class of combination vaccines against three infectious diseases in humans: diphtheria, pertussis (whooping cough), and tetanus.

• The MMR vaccine, is a vaccine against measles, mumps, and rubella.

What is the age of volunteers recruited for this vaccines combo trial?

The Pfizer-AstraZeneca is recruiting people over the age of 50 who may be at higher risk than younger people and have not been vaccinated already. Reuters quoted Matthew Snape, an Oxford vaccinologist who leads the trial, as saying that the initial results could guide subsequent vaccine deployment in the second half of the year.

"We will get some results through, we expect, by June or thereabouts that will inform the use of booster doses in the general population," he told reporters.

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Pfizer's COVID-19 vaccine arrives in Dubai on an Emirates SkyCargo fight.

What is the worst outcome of the combination shot?

It’s not known at this point. But the vaccines had already been proven both safe and effective in advanced clinical trials and on millions of people in the on-going global rollout — but only using the same shot within the prescribed gap.

Will there be more combo vaccine trials?

Potentially, yes. In December, Russia's Gamaleya Institute offered AstraZeneca the opportunity to use one of the two human adenoviral vector components of the Sputnik V vaccine in their clinical trials, according to Kirill Dmitriev, CEO of the Russian Direct Investment Fund (RDIF), which backs Gamaleya. Both AZD1222 and Sputnik V are administered in two doses, but where the former uses adenoviral vectors from chimpanzees, Sputnik uses human adenoviral vectors.

How will the immune response be measured?

Immune response is measured in a number of ways. One is in terms of specific cell functions ex vivo (cells isolated and studied in short- or long-term culture). Another is by measuring in vivo (within the living organism) responses of human subjects to a challenge from the pathogen (COVID-19). Data is gathered by measuring the changes in the concentrations of antibodies in the bloodstream or saliva, or measuring the incidence and severity of infections.

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