Enlarge /. COVID-19 vaccine at a vaccination center in Madrid on February 26, 2021.
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With worrisome variants of coronavirus seemingly popping up and spreading everywhere, leading vaccine manufacturers are wasting no time staying one step ahead of the growing threat.
This week, Moderna and partners Pfizer and BioNTech announced that they have started new clinical vaccine studies to increase the effectiveness of their approved vaccines against new SARS-CoV-2 variants – most notably B.1.351, a variant first identified in South Africa .
In a series of studies published last week in the New England Journal of Medicine, both the Moderna mRNA vaccine and Pfizer / BioNTech mRNA vaccine spurred antibodies in vaccinated individuals who neutralized the B.1.351 variant could. However, levels of these neutralizing antibodies were significantly lower than previous versions of the virus. (Both vaccines performed well against variant B.1.1.7, first identified in the UK and expected to become the dominant strain in the US next month.)
While vaccine manufacturers still expect current vaccines to protect against B.1.351 and other variants – at least to avert serious illness and death – they are preparing for the worst. The good news is that the design of the mRNA vaccine is relatively easy to adapt to the variants.
The variants carry dangerous mutations in critical areas of their spike protein, which seem to make the viruses more transmissible and more virulent than the original SARS-CoV-2. To adapt the current vaccines to the variants, all you need to do is edit the code of the spike mRNA molecule used in both vaccines to match the mutations in the variants. Moderna and Pfizer / BioNTech each stated that such adjustments could only take a few weeks.
But vaccine makers are starting their battle against the variants with an even simpler strategy: giving people a third shot of the current vaccines. It is believed that a third dose in addition to the current two-dose therapy could further increase levels of antibodies and other protective immune responses. As mentioned above, the data so far suggests that the vaccines stimulate the production of neutralizing antibodies against the variants – they are only present in relatively small amounts. A third shot – also known as a second booster – could raise the level further and increase protection.
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On Thursday, Pfizer and BioNTech announced that they had launched a trial testing the three-shot strategy. They are based on 144 people who were vaccinated six to 12 months ago in their Phase I study. After the third shot, companies will watch out for side effects and antibody levels in the participants. As the companies put it, the study will "evaluate" the boostability of the vaccine.
"While we have seen no evidence that the circulating variants are causing our vaccine to lose protection, we are taking several steps to act decisively and be ready should a strain become resistant to the vaccine's protection," said Pfizer CEO Albert Bourla said in a statement. "This booster study is critical to understanding the safety of a third dose and immunity to circulating strains."
In the meantime, the companies are also working on plans to launch a trial with a B.1.351-specific vaccine.
Moderna, meanwhile, is promoting its variant-specific vaccines. It has already produced a B.1.351-specific vaccine that it shipped to staff at the National Institutes of Health at the start of clinical trials. In addition, Moderna will test a combination vaccine that contains both the original vaccine and the B.1.351-specific component. After all, the company has already started a study testing a third shot of its current vaccine.
"As we try to defeat COVID-19, we must be vigilant and proactive when new variants of SARS-CoV-2 emerge," said Stéphane Bancel, CEO of Moderna, in a statement. “We are taking advantage of the flexibility of our mRNA platform and are quickly testing vaccine updates to 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. "
In advance of the results of this new round of testing, the US Food and Drug Administration released new guidance this week on how vaccine manufacturers can obtain approval for their updated vaccines. In short, the regulator made it clear that companies can submit data from smaller studies – compared to the massive ones they need to prove the effectiveness of their initial approvals. Studies may also focus on immune responses observed in participants to assess effectiveness, rather than number, of COVID-19 cases in vaccinated individuals compared to those in a placebo group.