A 3rd shot? A new booster? Vaccine makers rush to trials to beat variants

With disturbing coronavirus variants seemingly emerging and spreading everywhere, major vaccine makers are wasting no time trying to get ahead of the growing threat.

This week, Moderna and its partners Pfizer and BioNTech announced that they have launched new vaccine clinical trials aimed at boosting the efficacy of their licensed vaccines against new variants in SARS-CoV-2 – primarily B.1.351, an identified variant for the first time in South Africa.

In a series of studies published last week in the New England Journal of Medicine, the Moderna mRNA vaccine and the Pfizer / BioNTech mRNA vaccine stimulated antibodies in vaccinated people that could neutralize the B.1.351 variant. But the levels of these neutralizing antibodies were significantly lower than those seen against earlier versions of the virus. (Both vaccines performed well against variant B.1.1.7, first identified in the UK, which is expected to become the dominant strain in the US next month.)

While vaccine makers still expect current vaccines to protect against B.1.351 and other variants – at least to prevent serious illness and death – they are bracing for the worst. The good news is that the mRNA vaccine design is relatively easy to adjust compared to the variants.

The variants carry dangerous mutations in critical areas of their spike protein, which appear to make viruses more transmissible and virulent than the original SARS-CoV-2. Adjusting current vaccines to target variants simply involves modifying the code of the advanced mRNA molecule used in both vaccines to match the mutations of the variants. Moderna and Pfizer / BioNTech each said such adjustments could take just a few weeks.

But vaccine makers are starting their battle against variants with an even simpler strategy: give people a third dose of current vaccines. The idea is that a third dose in addition to the current two-dose regimen could further increase antibody levels and other protective immune responses. As mentioned above, the data so far suggests that vaccines stimulate the production of neutralizing antibodies against the variants – they’re just at relatively low levels. A third hit, i.e. a second booster, could further boost levels and increase protection.

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On Thursday, Pfizer and BioNTech announced that they had launched a trial to test the three-shot strategy. They are based on 144 people who were vaccinated six to 12 months ago in their Phase I trial. After the third shot, companies will monitor side effects as well as antibody levels in participants. As the companies say, the trial will “assess the booster potential” of the vaccine.

“While we have not seen any evidence that circulating variants result in a loss of protection provided by our vaccine, we are taking several steps to act decisively and be prepared in the event that a strain becomes resistant to the protection offered by the vaccine. vaccine, ”Pfizer CEO Albert Bourla said in a statement. “This booster study is critical to understanding the safety of a third dose and immunity against circulating strains.”

In the meantime, the companies are also working on plans to roll out a trial of a specific B.1.351 vaccine.

Moderna, meanwhile, is moving forward with its variant-specific vaccines. It has already manufactured a specific B.1.351 vaccine, which it sent to collaborators at the National Institutes of Health for the start of clinical trials. In addition, Moderna will also test a combination vaccine containing both the original vaccine and the component specific to B.1.351. Finally, the company has already started a trial testing a third injection of its current vaccine.

“As we seek to defeat COVID-19, we must be vigilant and proactive as new variants of SARS-CoV-2 emerge,” Moderna CEO Stéphane Bancel said in a statement. “By taking advantage of the flexibility of our mRNA platform, we are rapidly testing vaccine updates that address emerging variants of the virus in the clinic. Moderna is committed to making as many updates to our vaccine as necessary until the pandemic is under control. “

Ahead of the results of this new round of trials, the United States Food and Drug Administration this week released new guidance on how vaccine manufacturers could obtain approval for their updated vaccines. In short, the regulator has made it clear that companies can submit smaller trial data – compared to the massive trials they need to prove the effectiveness of their initial clearances. Trials may also focus on the immune responses seen in participants to gauge efficacy rather than the number of cases of COVID-19 in people vaccinated compared to those in a placebo group.