With worrying variants of the coronavirus apparently emerging and spreading everywhere, leading vaccine manufacturers are not wasting their time trying to anticipate the growing threat.
This week, Moderna and partners Pfizer and BioNTech announced that they have started new clinical vaccine trials with the aim of increasing the effectiveness of their authorized vaccines against new variants of SARS-CoV-2, mainly B.1.351, a variant identified by the first time in South Africa.
In a set of studies published last week in the New England Journal of Medicine, both the Modern mRNA vaccine and the Pfizer / BioNTech mRNA vaccine stimulated antibodies in vaccinated people that could neutralize variant B.1.351. But the levels of these neutralizing antibodies were significantly lower than what was seen in previous 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 U.S. next month.)
While vaccine manufacturers still hope that current vaccines will protect against B.1.351 and other variants – at least by preventing 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 adjust against variants.
The variants carry dangerous mutations in critical areas of their peak protein, which appear to make viruses more transmissible and virulent than the original SARS-CoV-2. Adjusting current vaccines to target variants involves simply editing the code for the peak mRNA molecule used in both vaccines to match the mutations in the variants. Moderna and Pfizer / BioNTech said such adjustments could take weeks to complete.
But vaccine manufacturers are beginning their battle against variants with an even simpler strategy: giving people a third injection of current vaccines. The thought 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 suggest that vaccines stimulate the production of neutralizing antibodies against variants – they are only at relatively low levels. A third shot – also known as a second boost – can increase levels even more and increase protection.
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On Thursday, Pfizer and BioNTech announced that they had started a trial to test the three-trial strategy. They are targeting 144 people who were vaccinated six to 12 months ago in their Phase I trial. After the third injection, companies will look at side effects as well as antibody levels in participants. As the companies put it, the test will “assess the potential” of the vaccine.
“Although we have seen no evidence that circulating variants result in the loss of protection provided by our vaccine, we are taking several steps to act decisively and be ready if a strain becomes resistant to the protection afforded by the vaccine,” Pfizer. CEO Albert Bourla said in a statement. “This reinforcement study is critical to understanding the safety of a third dose and immunity against circulating strains.”
In the meantime, companies are also working on plans to launch a test for a specific vaccine for B.1.351.
Moderna, for its part, is advancing with its specific vaccines for variants. It has already manufactured a specific vaccine for B.1.351, which it sent to employees of the National Institutes of Health to begin clinical trials. In addition, Moderna will also test a combined vaccine that contains both the original vaccine and the specific component 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. “Taking advantage of the flexibility of our mRNA platform, we are moving quickly to test 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. “
Before the results of this new round of testing, the Food and Drug Administration issued a new guideline this week on how vaccine manufacturers could obtain authorization for their updated vaccines. In short, the regulatory agency has made it clear that companies can send data from smaller trials – compared to the huge ones they needed to prove the effectiveness of their initial permits. The trials may also focus on the immune responses observed in the participants to assess the effectiveness, rather than the number of cases of COVID-19 in vaccinated people compared to those in a placebo group.