Experts suggest updating vaccines for new variants. How does it work & what are the challenges?

It is easier to update certain vaccine platforms than others, say experts

By Taran Deol
Published: Thursday 07 July 2022

Tailoring vaccines to protect against emerging SARS-CoV-2 variants is the latest consideration of the global medical world. But it is the easiest to update mRNA-based vaccines but less simpler for others, experts flagged. 

But there are ways to circumvent these challenges, scientists informed Down To Earth (DTE) amid official recommendations for updating vaccines. 

The United States Food and Drug Administration (FDA) has recommended including BA.4 and BA.5 components of Omicron in the updated versions of COVID-19 vaccines to be used as boosters in the country by fall this year. 

Following a public discussion on June 28, 2022, the decision was finalised on June 30, 2022 in the backdrop of these Omicron lineages marking their dominance in US and across the world. 

Studies have shown that COVID-19 vaccines have saved an estimated 20 million lives in the past year and while they continue to remain robust in preventing severe disease and death in the face of new emerging variants, their effectiveness is waning. 

“As we move into fall and winter, it is critical that we have safe and effective vaccine boosters that can provide protection against circulating and emerging variants to prevent the most severe consequences of COVID-19,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a June 30 statement.

This decision, however, can be a setback for vaccine manufacturers, who have till now been working on incorporating the BA.1 lineage of Omicron in their updated versions. On June 25, Pfizer Inc and BioNtech had stated their omicron-specific monovalent dose triggered a “substantially higher immune response against omicron BA.1 as compared to the companies’ current COVID-19 vaccine.” The companies claimed it can roll out these vaccines immediately. 

Along the same lines, Moderna Inc had stated its bivalent omicron vaccine had a “superior neutralising antibody response”. It reportedly has 200 million doses in the pipeline for early September. With the FDA now focusing on BA.4 and BA.5, it remains to be seen how this will impact the timelines. 

How are vaccines updated? 

It is easier for some platforms to change vaccines than others. “For the existing mRNA vaccine, it’s quite easy to change or add to the dose. That’s the whole benefit of this form of vaccine. It’s much harder for the others,” Annelies Wilder-Smith, from the Heidelberg Institute of Global Health, University of Heidelberg in Germany, told Down To Earth (DTE).

To update the mRNA vaccines, you replace the existing antigen with a new antigen and this can be done with any new pathogen as well. Essentially, two key ingredients are required — genetic sequence of the spike protein from a new variant of concern and a DNA template to build the mRNA. 

The former has already been published by scientists and is available. So, manufacturers need only to make the DNA template, which is a three-day process.

“By swapping out the genetic code of original spike protein for the one from this new variant, a new vaccine would induce antibodies that more effectively bind the Omicron virus and prevent it from infecting cells,” Deborah Fuller, a professor of microbiology at the University of Washington’s School of Medicine, wrote

She estimated it takes 52 days for manufacturers to produce and test enough doses of the updated vaccine for preclinical tests and another 100 days to conduct human trials.

Updating viral vector vaccines such as Janssen by Johnson & Johnson and AstraZeneca by the University of Oxford is also possible. Here, “genetic material from the COVID-19 virus is placed in a modified version of a different virus”. 

Once this enters our cells, the immune system is triggered. In June 2021, AstraZeneca launched a 2,800 participant study to test a beta-specific viral-vector vaccine as a booster dose.

While mRNA vaccines are the easiest to update, they are not the most widely administered across the world, according to Our World in Data. "The process of updating the AstraZeneca vaccine is similar to the mRNA candidates but requires extra steps to produce and purify the viral vector. This increases the amount of time needed to update the vaccine," said Fuller. She added:

The biggest potential issue with updating the AstraZeneca shot is that people previously immunised with this vaccine will develop immune responses to the carrier viral vector that could reduce immunogenicity in future doses. In this case, antibody responses against the ChAd5 carrier vector could interfere with its ability to deliver the code.

But there is a way to get around this hurdle. Studies have shown that people previously immunised with the AstraZeneca shot develop strong immunity when they are boosted with the mRNA vaccine.

It's still a better to update viral vector vaccines compared to protein-based vaccines such as Novovax, according to experts.

"It first has to go through a similar step as the mRNA vaccine (update the sequence) but unlike the mRNA vaccines (that are ready to go into arms once the sequence is updated), a protein based vaccine has to undergo additional time-consuming steps to get cells in the lab to produce the protein and then that protein has to be purified and validated to be intact," Fuller said. This increases the chances of the updated vaccines having less of a match with circulating strains.

It remains unclear what exactly the process will be for trialling and approving the updated vaccines. Influenza vaccines are also updated regularly, but fresh trials for it are not needed.

However, that is not entirely comparable with COVID-19 vaccines, since the former virus has been studied and understood for decades, while SARS-CoV-2 is barely three years old. 

The FDA has recommended updating the COVID-19 vaccines, but it appears that the chase of catching up with the mutating virus will continue. A year ago, delta was dominant the world and nobody expected Omicron to pop up. It’s likely we will be in a similar situation a few months down the road, said experts.

“The FDA clearly stated we want to be following the latest variant. But the whole point is to broaden the protection,” she added. 

We are now developing vaccines targeting BA.4 / BA.5, but it’s likely by December or January that we will have something else, Wilder-Smith said. 

For now, the way forward seems to be to use Omicron-specific vaccines as booster shots. It’s too dangerous to administer it as a primary dose, she added.

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