On Jun. 23, 2020, scientists at Scripps Research reported that some common strains of influenza have the potential to mutate to evade broad-acting antibodies that could be elicited by a universal flu vaccine. The findings highlight the challenges involved in designing such a vaccine, and should be useful in guiding its development.

In the study, published in Science, the researchers found evidence that one of the most common flu subtypes, H3N2, can mutate relatively easily to escape two antibodies that were thought to block nearly all flu strains. One of the main goals of current influenza research is to develop a universal vaccine that induces broadly neutralizing antibodies, also known as “bnAbs,” to give people long-term protection from the flu.

Although experiments and analyses suggested that H3N2 viruses are broadly capable of developing resistance mutations, the same was not true for H1N1 viruses. The researchers tested several H1N1 viruses and found that none seemed able to mutate and escape, except for rare mutations with weak escape effects. The H3N2 and H1N1 subtypes account for most of the flu strains circulating in humans.

The researchers used structural biology techniques to show how differences in the hemagglutinin stem structure allow H3N2 flu viruses to develop resistance mutations to the two stem-binding antibodies more easily than H1N1 viruses.

The researchers now plan to conduct similar studies with other flu subtypes and bnAbs. They say that in principle, a vaccine eliciting multiple bnAbs that attack different sites on flu viruses or are more accommodating to changes in the virus could help mitigate the problem of resistance mutations.