COVID vaccine researchers do the two-step as new variants emerge

By Mark Lynas

January 25, 2021

For a world desperate for billions of doses of effective COVID vaccines to end the ongoing pandemic, it seems like one step forward and two steps back.

On the same day that pharmaceutical giant Merck announced that it was discontinuing its own COVID vaccine effort due to lack of efficacy, vaccine manufacturer Moderna warned that its current shot was likely less effective in tackling the new variant that has emerged in South Africa.

However, Moderna did also say that it is launching a new trial for an improved booster of its mRNA vaccine that has been tweaked to account for the genetic mutations seen on the new COVID virus variants.

“Out of an abundance of caution and leveraging the flexibility of our mRNA platform, we are advancing an emerging variant booster candidate against the variant first identified in the Republic of South Africa into the clinic to determine if it will be more effective to boost titers against this and potentially future variants,” Stéphane Bancel, chief executive officer of Moderna, said.

A “titer” is a measurement of the concentration of antibodies in blood serum. Moderna says that it observed a six-fold reduction in neutralizing titers against the new B.1.351 variant of the SARS-CoV-2 virus as compared to earlier variants with its current mRNA-1273 vaccine.

If these results also hold outside the laboratory, this means that Moderna’s current vaccine may be substantially less effective in preventing people from catching and spreading COVID-19 if they are exposed to new variants.

This is particularly worrying because the new South African B.1.351 variant, and a new United Kingdom variant named B.1.1.7, seem to be substantially more infectious than earlier variants, and may also be more lethal. Fortunately, Moderna’s current vaccine was observed to retain full effectiveness against the new UK variant.

In this it performs similarly well to the other mainstay mRNA COVID vaccine, manufactured by Pfizer/BioNTech. A preprint study conducted by Pfizer/BioNTech scientists has already found that its vaccine seems to retain full efficacy against the B.1.1.7 UK strain. It did not, however, assess efficacy in response to the South African variant.

Experts around the world are scrambling to sequence more SARS-CoV-2 genomes so the pattern of emerging variants can be better understood. Governments are also rushing to close borders and institute full mandatory quarantine for international travelers in order to stop newer, more infectious variants from quickly becoming dominant worldwide.

First detected in September 2020 in the United Kingdom, the SARS-CoV-2 B.1.1.7 variant has 17 mutations in the viral genome with eight mutations located in the spike (S) protein. The B.1.351 variant, first detected in South Africa, has 10 mutations located in the spike (S) protein.

Moderna’s vaccine — and most others approved for COVID-19 — target the spike protein, so the higher number of mutations on the South African B.1.351 variant may account for the vaccine’s reduced efficacy.

However, the mRNA technology utilized makes it relatively quick and easy to tweak the genetic sequence of the vaccine in order to account for and target any new mutations — a substantial advance on older vaccine technologies.

Moderna has accordingly developed an emerging variant booster candidate (mRNA-1273.351) against the B.1.351 variant first identified in South Africa. This is being advanced into preclinical studies and a Phase 1 study in the United States to evaluate the immunological benefit of boosting with strain-specific spike proteins.

Less encouraging was today’s announcement by the pharmaceutical giant Merck that it is dropping its own COVID vaccine efforts due to low levels of efficacy seen in its vector-based vaccine candidate.

Merck reported that its V590 and V591 vaccine candidates, while generally well tolerated, showed inferior immune responses in Phase 1 clinical trials as compared to those seen for other COVID vaccines. The company did not provide further details at this stage but said that the results of its Phase 1 studies on V590 and V591 would be submitted to a peer-reviewed journal.

Moderna said its findings would also be submitted to a peer-reviewed journal. However, in the meantime a draft manuscript has been published on the preprint site bioRxiv.

Image: NIAID