Booster race: Heat is on to 'tweak' vaccines against COVID variants

Two are mRNA-based (Pfizer, Moderna); two are attenuated/vector-based vaccines (AstraZeneca, J&J).

Also, a new shot being developed by the US Army is touted as a “super vaccine” against all SARS variants, including SARS-CoV-1 (first seen in 2003), though its first rollout remains iffy.

How soon will the "updates" be available? How safe/effective are these new shots? Here’s what we know so far:

What COVID vaccine 'tweaks' had been announced?

Pfizer announced its “updated” vaccine specifically against the Omicron variant will be available by March 2022.

Johnson & Johnson announced it is working on an Omicron-specific vaccine, too. An AstraZeneca scientist has announced in December that it has taken steps to target Omicron with a booster.

On Wednesday (January 11, 2022) Moderna, too, has announced it is working on an “updated” shot for Omicron.

Scientists say current vaccines still work. When used as a booster, they are still protective against the new variants, even if they're based on the “wild type” virus first seen in Wuhan, China, two years ago.

But the power of the current jabs may be declining, according to Science. In the current race to update vaccines, there’s no clear front-runner — yet. Sandy Douglas, from Oxford University, says its updated vaccine being developed with AstraZeneca could “respond to any new variant more rapidly”.

What’s the approval process for vaccine “updates"?

Vaccines are approved by health regulators in various jurisdictions. For example, the US FDA follows a standard process for reviewing the quality, safety and effectiveness of medical products.

Results of three phases of clinical trials must show a vaccine candidate to be both safe and effective. Drug trials, closely supervised and using the gold standard of tests — double blind, placebo-control and randomised — take time. It typically involves several thousand people on both “arms” (vaccine and placebo arms).

Germany-based BioNTech, Pfizer’s development partner, said it can adapt its mRNA vaccine “within six weeks” and ship initial batches “within 100 days”.

A company executive also added they are “rapidly” advancing an Omicron-specific shot that could move from the lab to human testing “in only 60 to 90 days”.

How are conventional vaccines manufactured?

Conventional vaccines usually contain weakened or inactivated disease-causing organisms or pathogen proteins (antigens) to stimulate the immune response of the body, which is prepared to react faster and more effectively if it is exposed to the infectious agent in the future.
Production of conventional viral vaccines in bioreactors is a well established process, though lengthy and cumbersome: it includes several steps:

Also, the handling of large volumes of live virus is necessary.

How do mRNA vaccines differ from conventional vaccines?

Messenger ribonucleic acid (mRNA) vaccines form a new technology. Conventional vaccines contain viral proteins or disabled forms of the virus (live attenuated and inactivated pathogens) that trigger an immune response from the body against infection.

mRNA delivered to human cells produce a protein that acts as the antigen (foreign molecule) when triggers an immune response. Convetional vaccines have been effective against a wide variety of pathogens, but not against infectious diseases, such as cancer. It required more potent and versatile vaccine platforms, and mRNA vaccines are seen as the answer.

What’s the advantage of mRNA vaccine?

It’s in the preparation and mass production that give mRNA an edge. To trigger an immune response, most vaccines put a “weakened” (attenuated) or “inactivated” (killed) whole germ into our bodies.

That’s how vaccines have always worked since 1798, with Edward Jenner’s invention of the smallpox vaccine.

In this COVID pandemic, the mRNA technique found its prime time. instead of killing or weakening viruses, mRNA to teach our cells how to make a protein, or a piece of it, using a code or “blueprint” of a specific trait of a viral antigen, the molecule that elicits immune reaction.

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In this COVID pandemic, the mRNA technique found its prime time. instead of killing or weakening viruses, mRNA to teach our cells how to make a protein, or a piece of it, using a code or “blueprint” of a specific trait of a viral antigen, the molecule that elicits immune reaction.

Once injected, it then trains our body to elicit an immune response (generating antibodies, memory B cells and killer T cells) when we contract the real virus — thus allowing us to immediately fight it off.

How was the mRNA vaccine developed?

Hundreds of scientists have worked for decades to develop mRNA vaccines. It began in the early 1960s but the technique to deliver the mRNA molecule into cell was discovered only in the 1970s. The experiments of Robert Malone, an American virologist and immunologist, in 1987 made him realise that if cells could create proteins from mRNA delivered into them, it might be possible to treat RNA as a drug.

Biochemist Katalin Karikó and immunologist Drew Weissman, founders of a start-up called RNARx, made a key finding to help synthetic mRNA to evade the cell’s immune defences.

That led to the development of the vaccine delivery system of a co-formulation of the RNA encapsulated in lipid nanoparticles (LNPs) that protect the RNA strands and help their absorption into the cells.

Which was the first mRNA vaccine?

The first mRNA vaccines using fatty envelopes were developed against the deadly Ebola virus. Since that virus was only found in some African countries, it had no commercial development in the U.S.

Which are the widely used mRNA vaccines?

Currently vaccines for COVID-19, Pfizer-BioNTech’s Comirnaty and Moderna mRNA-1273 are the only approved mRNA vaccines.

How are mRNA vaccines manufactured?

RNA vaccines and conventional vaccines take different manufacturing routes. The mRNA vaccines manufacturing process is its biggest advantage, say experts.

A vaccine based on mRNA, by definition, is much faster and simpler to manufacture than conventional jabs, as only the “blueprint” — and not the antigen itself — needs to be produced.

Taken together, the rapid development of the COVID-19 vaccines did not come out of the blue at all — the current COVID-19 pandemic merely provided momentum for mRNA vaccines to speed up their progress to approval

- Rein Verbeke, pharmaceutical scientist specializing in mRNA vaccines, Ghent University in Belgium

In general, it takes a week to generate an experimental mRNA batch. Once a decision is taken, this allows developers to test it in animals first (pre-clinical phase), then on humans (clinical phase) very quickly.

An mRNA vaccine consists of a strand of mRNA that codes for a disease-specific protein (antigen, the molecule that elicits immune response).

To "boost” the integration of this blueprint mRNA in the body cells and to increase vaccine stability, the mRNA is carried by “containers” — in the form of certain fatty substances (lipids) — lipid polyplexes form LNPs.

Upon injection, the lipid nanoparticles protect the mRNA from “degradation” and help it reach the cells where the code contained in the mRNA strand is “read” to produce the "antigen”, a protein that eventually triggers the desired immune response.

Here’s the interesting part: After injection, our cells break down mRNA and get rid of it — typically within a few days. Scientists estimate that the spike protein, like other proteins our bodies create, may stay in the body up to a few weeks.

It’s not clear at this point if animals tests would still be required for the “updates” to approved vaccines.

Can new mRNA vaccines be stored/distributed at room temperatures?

Not yet. “Super-cooling” remains a key requirement for transport and storage of mRNA vaccines — from Moderna and the Pfizer/BioNTech. This costly “cold chain” is a must before the vaccines end up in the arms of people. This poses a major obstacle, not only increases cost and the shipping complexity; but also cuts off access to remote communities without reliable electricity or refrigeration.

Why is mRNA vaccine super cooling required?

The reason for these frigid conditions is that the key vaccine ingredient— messenger RNA (mRNA) molecules — is extremely fragile. Storage at extremely cold temperatures slows down the chemical reactions that can tear it apart.

Is there a way around this supercooling problem?

Not at the moment. But work is underway to reduce this freezing requirement, according to a recent report. One way is to tinker with the mRNA structure; another is by shipping the vaccine in solid form with a sugary “protectant”. These solutions are “promising”, and could play an important role in arresting the current pandemic.

What is the future of mRNA technology?

Today, it’s easy to forget that vaccines used to take a minimum of 4 years to develop (with the mumps vaccine) — some took as many as 16 years. With COVID, vaccines took less than 12 months to get through “warp speed” development.

Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273 were given the first historic authorisation for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing.

In a 2018 article, the journal Nature called mRNA vaccines as “a new era in vaccinology” — and as worked extremely well in protecting tens of millions of people and, that too, with a good safety record.

“Taken together, the rapid development of the COVID-19 vaccines did not come out of the blue at all — the current COVID-19 pandemic merely provided momentum for mRNA vaccines to speed up their progress to approval,” Rein Verbeke, a pharmaceutical scientist specialising in mRNA vaccines at Ghent University in Belgium, wrote with his colleague in the J Controlled Release.

COVID created the momentum for mRNA: it has proven to be a “miracle”. With mRNA, it appears a speedier response to the highly contagious SARS-CoV-2 variants, including Omicron, is now made possible.

Convetional vaccines have been effective against a wide variety of pathogens, but not cancer. It required more potent and versatile vaccine platforms, and mRNA vaccines are seen as the answer.