Why You Can’t Read Too Much Into the Virus-Mutation Research

Vaccine effectiveness against variants comes down to individual mutations, but it’s important to take a big-picture view

Photo: BSIP/UIG Via Getty Images

By now you’ve most likely heard about the major coronavirus variants circulating around the globe: B.1.1.7, the variant first identified in the U.K., and B.1.351, first identified in South Africa. These variants are concerning because they are more transmissible. This characteristic, along with others they may have, are not fully understood, but they are rooted in point mutations: single-letter changes in the genomes of the virus.

The point mutation N501Y, for example, refers to a change in the virus genome at position 501, from amino acid N (asparagine) to the amino acid Y (tyrosine). N501Y is a point mutation you will likely be hearing about a lot because it’s been associated with tighter binding of the virus to human cells.

Scientists are studying the point mutations in these variants in order to gauge the effectiveness of our current vaccines against them. On Monday, researchers from the University of Texas published a paper in Nature Medicine showing the effect of some of these point mutations on the ability of the Pfizer/BioNTech vaccine to neutralize the virus, prompting optimistic headlines about its effectiveness against coronavirus variants.

The researchers engineered viruses containing key point mutations in the U.K. variant (Δ69/70 + N501Y + D614G) and South African variant (E484K + N501Y + D614G) and tested the vaccine against them. They found that the vaccine’s ability to neutralize the virus with the mutations seen in the South African variant was slightly lower than its ability to neutralize the virus with the U.K. mutations, but they emphasize that these differences are very, very small. In other words, the data suggests that the Pfizer vaccine offers protection against variants with these specific point mutations.

Therein lies an enormous caveat: The U.K. and South African variant have the key mutations studied in the paper, but they also contain numerous other point mutations that were not studied. For this reason, tweeted Eric Topol, MD, chair of innovative medicine at Scripps Research, this report on the variants is “unhelpful.”

“Looking at virus neutralization of engineered point mutations ignores the extensive gene-gene interactions (the company it keeps),~20 mutations (~10 in spike), for each variant,” he wrote on Monday.

This means that studying the effectiveness of vaccines against individual mutations, or small combinations of them, does not give useful information about the effectiveness of the vaccines in real life, where the variants that are circulating carry many more point mutations whose effects and interactions are not known.

Topol’s point is an important one to keep in mind as you come across news about variants. While individual point mutations and their effects are useful for understanding a variant’s biology, remember that in the wild, variants can have many mutations, and they may not act alone.

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