Science: New challenges in flu vaccine

thetheory that a vaccine that triggers multiple bnAbs (broad neutralizing antibodies) to attack different parts of the influenza virus, or that is more adapted to changes in the virus, could help alleviate the problem of drug-resistant mutationsin 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 strains of influenza viruses may have mutations to escape the wide-ranging antibodies caused by the universal flu 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 InstituteIn 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 broad neutralizing antibodies , bnAb , to protect people from long-term infection seisfrom influenza viruses"These results suggest that when we design a universal influenza vaccine or develop 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 DrIan Wilson,'s communications author and director of the Scripps Research Department's Department of Integrated Structural and Computational Biology"the prospect ofuniversal vaccine
flu kills millions of cases and hundreds of thousands of people worldwide each year Flu viruses have long been a challenge for vaccine designers because they can mutate quickly and vary greatly from strain to strain The combination of strains transmitted among people tends to change during each flu season, and existing flu vaccines can only produce immune for a small number of recently transmitted strains As a result, the current vaccine provides only partial and temporary quarter-by-season protection Still, scientists have been working on the development of a universal flu vaccine that provides long-term protection by inducing immune responses, including bnAbs Over the past decade, several research groups, including Wilson, have found and analyzed the properties of several neutralizing antibodies during the recovery of influenza patients But the extent to which pandemic influenza viruses can escape these babs by simply mutating has not been fully studied In the study, written by postdoctoral research assistants Dr Nicholas Wu and Dr Andrew Thompson, the team first looked at whether the H3N2 influenza virus could escape neutralise the role of two more promising flu babs found so far The two antibodies, CR9114 and FI6v3, bind to a key area of the viral structure called hemagglutin stem, which does not change much between strains Because they are broadly resistant to different influenza strains, they are thought to be antibodies that should be induced by a universal influenza vaccine and are key to future treatment of severe influenza infections Using genetic mutations to systematically alter one protein amino acid structure at the binding point of bnAbs, Wu and his colleagues found a number of single and double mutations that allowed the H3N2 influenza virus to escape the infection-blocking effects of antibodies The team also found some examples of this "drug-resistant mutation" in a database of genetic sequences from pandemic influenza strains, suggesting that the mutation has occurred occasionally in a small fraction of the common influenza virus Different influenza virus strains have different escape skills
H3N2 and H1N1 subtypes account for most influenza strains that are transmitted in humans Although experiments and analyses have shown that the H3N2 virus has a wide range of resistance mutations, this is not the case with the H1N1 virus The researchers tested several H1N1 viruses and found that, in addition to a rare mutation with a weak escape effect, no virus appeared to be able to mutate and escape Using structural biology techniques, the researchers demonstrated how differences in the structure of hemagglutinin stems make the H3N2 influenza virus more likely to produce an anti-mutation against the two stem regions than the H1N1 virus bnAbs is a prototype antibody that should be induced by a universal influenza vaccine, and if H3N2 can escape bnAbs relatively easily, then we may need to consider more carefully and rigorously the design of a generic influenza vaccine for certain influenza subtypes," Wu said "The good news is that a universal flu vaccine should at least be effective for the H1N1 subtype." Researchers now plan to conduct similar studies of other flu subtypes and bnAbs In theory, they say, a vaccine that triggers multiple bnAbs attacks different parts of the flu virus, or is more adapted to changes in the virus, could help alleviate the problem of drug-resistant mutations