Better bivalent vaccine in the wings

Public interest in getting more covid shots may be waning, but Australian scientists are still working on new formulations and delivery methods.

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Pfizer’s BA.4/5 bivalent vaccine will be the one to try and get in stock for covid jab number five, but the more plentiful BA.1 bivalent is still a good option, according to infectious disease clinician Dr Paul Griffin.

Speaking at the Royal College of Pathologists of Australasia conference in Melbourne on Sunday, Dr Griffin said that the timing of ATAGI’s decision to allow fifth booster doses was unfortunate.

The announcement came earlier this month and took effect on 20 February.

In January, the TGA provisionally approved Pfizer’s BA.4/5 vaccine, which has been updated to include 15mcg of mRNA encoding the BA.4/5 omicron subvariant spike protein.

Stocks won’t arrive until 6 March, leaving a two-week gap between the start of the fifth booster rollout and first supply of the most up-to-date vaccine. The government announced today it had ordered a further three million doses to arrive in April.

In the meantime, the more readily accessible vaccine is Pfizer’s BA.1 bivalent formulation, which uses a spike protein from the sublineage of the original Omicron variant.

“The BA.1 is at least a little bit better than the original vaccines against even some of the more recently circulating variants, with safety that’s essentially the same as the original,” Dr Griffin said.

“The BA.4/5 bivalent is probably a little bit better again, but it gets harder and harder to measure these things in studies, [because] these days there are a lot more confounders.”

In general, he said, the BA.4/5 vaccine is about 20% more effective than the original vaccine in terms of protection against the BA.4/5 Omicron variant, and will most likely afford better protection against the currently circulating variants.

Dr Griffin was fairly certain that boosters would become a yearly event, especially as technology develops and current vaccines are improved upon.

He said ideally we would have a vaccine that was better at preventing infection.

“But then there are things like protecting against all pending variants, having a shelf life that’s a lot longer … and conditions that are less challenging to maintain,” he said.

Several novel approaches are being tested and developed in Australia.

Early on in the pandemic, the University of Queensland had a promising vaccine candidate that used a molecular “clamp” to keep proteins in the correct shape.

The particular molecular clamp chosen was glycoprotein 41, a HIV protein, which caused recipients to test falsely positive for HIV.

A new version of the molecular clamp vaccine is set to enter clinical trials “any day now”.

There’s also an oral vaccine in the early phase of clinical trials, which Dr Griffin likened to drinking a probiotic.

“Instead of using a viral vector to transport the instructions we need to make those spike proteins, those instructions were put in a modified Bifidobacterium, B. longum,” he said.

The idea is that the resulting spike proteins will then be presented at a mucosal surface, fostering better mucosal immunity.

An intranasal vaccine is also in the works, using an adenovirus vector that has been modified so that it can reproduce once.

“That single cycle of replication means you get about 100 times more spike protein produced,” Dr Griffin said.

“One of the challenges of intranasal route is it’s often hard to get a strong enough response, so the thought was that this strategy might overcome that.”

Dr Griffin also said that, while most of these innovative vaccines are likely just a year away, education remains the most important method to keep covid under control.

“Addressing misinformation, complacency and looking at the coverage of vaccines as we see our booster rates drop off is going to be one of the most important things we can do,” he said.