Influenza B virus, cut-away illustration. Influenza (flu) is a respiratory disease caused by infection with a flu virus. Influenza spreads around the world every year causing seasonal outbreaks, resulting in about three to five million cases of severe illness and about 250,000 to 500,000 deaths. Influenza B is a type of flu that is similar to influenza A and contributes to the annual seasonal flu outbreak. Influenza B viruses only pass from human to human, unlike type A where there are strains of virus in animals such as bird flu or swine flu.
Credit: Roger Harris / Science Photo Library
Scientists at the Institute for Biomedical Sciences at Georgia State University, Atlanta, GA, USA believe they have produced a vaccine that is effective against different strains of the influenza B virus and think they may be able to extend this to include the Influenza A strains. They were able to do this because they understand how the influenza viruses evolve to escape our immune systems.
Influenza B viruses are often the dominant strains in seasonal flue epidemics accounting for about a quarter of clinical infections. As the Georgia State University news release explains:
Influenza epidemics pose a major threat to public health, and type B influenza has coincided with several severe flu outbreaks. About one-fourth of clinical infection cases are caused by influenza B viruses each year. Influenza B viruses are sometimes the dominant circulating strains during influenza seasons, such as the 2019-20 U.S. flu season when influenza B caused more than 50 percent of the infections.The problem with the current vaccines is that they usually produce antibodies against the 'head' proteins of the influenza viruses, but these proteins can evolve, without detriment to the virus, so they can escape recognition by our immune system that the vaccines have 'programmed' to look for specific proteins. However, there are other regions of the virus that are more essential to the virus and so are highly conserved during natural evolution since mutations in the RNA that codes for them tend to be quickly eliminated. One such region is the so-called 'hemagglutinin (HA) stalk'.
In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates. We found that layered protein nanoparticles incorporated with structure-stabilized constant antigens have potential as a universal influenza vaccine with improved immune protective potency and breadth.
Our next aim is to combine the influenza A nanoparticles from our previous study with the influenza B nanoparticles we have fabricated and tested here to create a multivalent universal influenza nanoparticle vaccine against both influenza A and B
Professor Baozhong Wang, senior author
Institute for Biomedical Sciences
Georgia State University.
Institute for Biomedical Sciences
Georgia State University.
Influenza B has two lineages that are genetically distinct and trigger different immune responses. Seasonal flu vaccines are developed with one or both lineages of influenza B viruses, but they’re limited by the ability of circulating strains to escape the immune system or vaccination. These vaccines are often ineffective because the variable portion of the influenza virus (the HA head) evolves. As a result, seasonal influenza vaccines need to be reformulated and updated frequently. To overcome these limitations, a universal influenza vaccine containing conserved parts of the virus and providing substantial broad cross-protection against diverse virus strains is urgently needed.And that means that vaccines against these conserved proteins will also be effective against different lineages and strains that will very probably share these proteins.
The Georgia team have developed a harmless double-layered protein nanoparticle constructed from a stabilized portion of this hemagglutinin protein which, when injected will provoke an immune response against any virus which has that protein in its stalks.
The nanoparticles were tested on mice and in cell cultures where they were found to be effectively taken up by dendritic cells - an important stage in the production of an immune response against pathogens - and were found to be “biocompatible, biodegradable and highly immunogenic in animals”. In other words, it has no harmful or toxic effects, is naturally degraded by the body and produces a strong immune response.
Sadly, the team's paper in Biomaterials is behind a paywall but the abstract can be read here. In it the authors say:
In this study, we generated structure-stabilized HA stalk antigens from influenza B and fabricated double-layered protein nanoparticles as universal influenza B vaccine candidates. In vitro studies found that the resulting protein nanoparticles were effectively taken up to activate dendritic cells. Nanoparticle immunization induced broadly reactive immune responses conferring robust and sustained cross-immune protection against influenza B virus strains of both lineages.The theory of evolution is of course, fundamental to this sort of research since it explains why viruses are in a continuous arms race with our immune systems and why some parts of an organism are conserved and so are shared by organisms with a common ancestry, while other parts can mutate and change to give new strains, subspecies and species.
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