This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Influenza viruses constantly shapeshift to evade recognition by the immune system. This shapeshifting occurs in critical proteins like hemagglutinin (HA), which controls how the virus attaches to human cells before entering them.
Influenza viruses can evade immunity in two major ways: through the gradual accumulation of mutations that make HA harder for the immune system to recognize or through reassortment events that can introduce substantially different viral proteins and potentially lead to flu pandemics. To address this challenge, seasonal flu vaccines remain the primary approach because they can be developed to target the flu viruses circulating most predominantly in a given season. Now, in a Nature Communications study published Aug. 13, 2026, scientists at Scripps Research offer a blueprint for stabilizing the various versions of influenza's HA protein and using it to build nanoparticle vaccine candidates.
Influenza is the latest target made compatible with the nanoparticle technology, specifically called self-assembling protein nanoparticles (SApNPs), which work by organizing many copies of viral proteins into clusters that the immune system can more easily recognize. This framework could eventually be applied to inform the design of next-generation vaccines across diverse flu viruses. "Influenza HA is naturally poised to change shape by design because it needs to undergo a dramatic structural change during viral entry," says senior author Jiang Zhu, a professor at Scripps Research.
"What I'm trying to do is to find a magic trigger that, no matter what flu strains come along, mutating that trigger will make a stable antigen that can be used in a nanoparticle vaccine." Influenza viruses cause up to 5 million cases of severe illness and claim between 290,000 and 650,000 lives worldwide each year, while four major pandemics since 1918 have caused tens of millions of deaths. Most commercial flu vaccines are produced with an old-school method: growing them in chicken eggs. But vaccine development may now be shifting from egg-based production toward more modern methods that use nucleic acids—like the mRNA found in COVID-19 vaccines—and proteins, which offer greater flexibility, efficiency and scalability.
On the surface of the influenza virus, groups of three identical HA proteins form bundles known as trimers. Many of these HA trimers are distributed across the viral surface, where they coordinate binding and entry into human cells. Because vaccines train the immune system to recognize viral proteins, scientists must find ways to generate stable versions of these proteins in the lab.
But HA trimers often misfold or fall apart when exposed to temperature changes or acidic conditions. In the new study, Zhu and his team set out to make stabilized versions of the HA trimer. They began with an observation: Across many different flu viruses that infect humans, birds and pigs, which all contain different versions of the HA protein, there was a specific location—the 95th amino acid—that was consistently water-loving.
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