Science: New research suggests that the design of a universal flu vaccine may be more challenging than expected.

, June 27, 2020 /
--- BioON/--- in a new study, researchers from the Scripps Research Institute, fred-Hutchinson Cancer Research Center, the University of Washington and Hong Kong, China, have found that some common flu virus strains may mutate to escape wide-ranging antibodies caused by theof the universalflu vaccineThese findings highlight the challenges of designing such vaccines and should help guide vaccine developmentThe findings were published in the June 19, 2020 issue of The Journal of Science under the title "Sert genetic barriers for resistance to HA stembodies anti-anti-anti-influenza H3 and H1 viruses"The paper's lead authors are DrNicholas Wu, a postdoctoral researcher at the Scripps Institute, and DrAndrew Thompson, a researcher at the Scripps Institutepicture from CC0 Public Domainin the study, the researchers found evidence that H3N2, one of the most common influenza subtypes, can mutate relatively easily to escape two antibodies that are thought to block almost all influenza virus strainsHowever, they found it much more difficult to escape antibodies that also have a wide range of neutralizing effects for another common subtype, H1N1one of the main goals of current influenza research is to develop a universal vaccine that induces a wide range of neutralizing antibodies, bnAb, to protect people from influenza virus infection for a long time"These results suggest that when designing a universalinfluenza vaccineor developing a universal influenza treatment using bnAb, we need to figure out how to make it harder for the flu virus to escape with a resistance mutation," said Dr Ian Wilson, paper's communications author and director of the Scripps Research Department's Department of Integrated Structural and Computational Biology "the prospect of a universal vaccine flu causes millions of illnesses and hundreds of thousands of deaths around the world every year Flu viruses have long posed a challenge for vaccine designers because they can mutate quickly and vary widely from strain to strain each flu season, the combination of strains circulating in the population tends to change, and the existing flu vaccine can only induce immunity to the most recently circulated strains As a result, the current vaccine provides only partial temporary seasonal protection , however, scientists have been working on the development of a universal flu vaccine that provides long-term protection by inducing immune responses, including bnAb Over the past decade, several research groups, including Wilson's team, have found ab, which targets multiple influenza strains, in recovering influenza patients and analyzed their characteristics However, there is not enough discussion about the extent to which circulating influenza viruses can mutate to escape these bnAbs in the study, the researchers looked at whether the H3N2 influenza virus could escape the neutrality of two of the more promising anti-flu babs that have so far been found these two antibodies, called CR9114 and FI6v3, bind to a key region of the influenza virus's structure called hemagglutin stem, which varies little from strain to strain Because they have extensive neutrality and activity with different influenza strains, they are conceived as antibodies that should be able to cause a universal influenza vaccine, and are also thought to be an ingredient in future treatments for severe influenza virus infection Wu and his colleagues used genetic mutations to methodically alter amino acids in the hemagglutinin backbone of the two bnAb antibodies, and found that many single and double mutations allowed the H3N2 flu virus to escape the infection blocking effects of these antibodies they also found some examples of these "resistance mutations" in the genetic sequence database of circulating influenza virus strains, suggesting that they have occurred occasionally in a small number of common influenza viruses escape skills vary from influenza virus strain although experiments and analysis have shown that the H3N2 virus is generally capable of producing resistance mutations, this is not the case for H1N1 viruses The researchers tested several h1N1 strains and found that none of the H1N1 strains appeared to be able to mutate and escape, except for a handful of mutations with a weak escape effect H3N2 and H1N1 subtypes account for most of the influenza strains circulating in humans the researchers used structural biology techniques to show how differences in the structure of the hemagglutinin backbone make the H3N2 influenza virus more likely to produce an anti-mutation of the two antibodies that bind to the hemagglutinin trunk than the H1N1 influenza virus "If H3N2 is more likely to escape these bnAbs, which are the archeatocies that universal influenza vaccines should induce, then we may need to think more carefully and rigorously about the design of a universal influenza vaccine for certain influenza virus subtypes," Wu said The good news is that the universal flu vaccine should at least be good against the H1N1 subtype "
these researchers now plan to conduct similar studies on other influenza virus subtypes and bnAb In principle, they say, a vaccine that can cause multiple attacks on different sites on the surface of the flu virus or that is more adaptable to changes in the flu virus could help alleviate the problem of resistance mutations (Bio Valley Bioon.com) References: Nicholas C Wu et al , Dywed dh'r rhoi to HA stem antibodies in influenza H3 and H1 viruses Science, 2020, doi: 10.1126/science.aaz5143.
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