Vienna researchers tested an additional antigen for the influenza vaccine

Scientists in Vienna want to improve the effectiveness of influenza vaccines by using another antigen in addition to hemagglutinin. They used neuraminidase, a second major component on the viral surface, to create virus-like particles. In a limited animal experiment, the candidate vaccine protected mice from influenza, which was fatal to them.

Acute courses of influenza

“The World Health Organization (WHO) estimates that there are still one billion cases of seasonal flu each year, with three to five million severe cases and about 500,000 deaths. 60 percent, it is the production of neutralizing antibodies (the body’s own; reference) against influenza hemagglutinin (HA). based, but ignores neuraminidase (NA) as a major target on the (virus) surface,” Leticia Guzmán Ruiz wrote now. His co-authors, including the Institute of Molecular Biotechnology (IMBA) and the University of Natural Resources and Life Sciences (BOKU) in Vienna, and biotechnologist and vaccine researcher Florian Krammer (Icahn School of Medicine/New York), recently professor of infectious disease. Medicine in Meduni Vienna.

Influenza viruses are characterized by their two surface proteins – hemagglutinin (HA or H) and neuraminidase (NA or N). Influenza A viruses that are most important pathogens in humans have surface H1 (eg A/H1N1), H2, H3, H5 (eg H5N1 “bird flu”), H7 or H9. N1 and N2 are the major types of neuraminidase. Current vaccines prepared from chicken embryos or cell cultures are designed for the most common virus subtype (influenza A) every year according to WHO recommendations. Vaccines currently contain two hemagglutinin antigens (H1 and H3) for A/H1N1 and A/H3N2. To date, less attention has been paid to the neuraminidase antigens (N1 and N2 for the two virus strains identified; ref.).

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Animal experiments with mice

So Vienna scientists used genetic engineering (insect cell systems) to produce N2 antigens in virus-like particles (VLPs). Such particles – in this case based on the HIV-1 structural protein (Cag) – have long been used as antigen carriers for vaccines, which are now used billions of times around the world. Vaccines against HPV (cervical cancer, genital warts, etc.) are an example. VLPs containing antigens elicit an increased immune response with the generation of antibodies compared to antigens alone. This is based on their virus-like “appearance” when recognized by the immune system.

In animal experiments, groups of five mice each received one microgram of N2-VLP constructs twice, 0.3 micrograms of either soluble N2, VLPs lacking surface neuraminidase, or completely irrelevant protein. Four weeks later, an artificial infection with the A/H3N2 influenza virus strain was performed. “Mice that received a vaccine of one microgram of N2 VLPs were completely protected from fatal disease, but lost 15 percent of their body weight,” the scientists wrote in “Frontiers in Immunology” ( /10.3389/). fimmu.2024.1425842). In contrast, all animals that received only soluble N2 proteins without synthetic virus-like particles died. VLPs with N2 at a low dose (0.3 micrograms) per inoculum survived for the most part with significant weight loss. Small rodents such as mice or ferrets have been used as model organisms for influenza research, including vaccine development, for decades.

While discussing their results, the scientists note that in the future, VLPs with additional neuraminidase proteins or surface neuraminidase could also be used for influenza vaccines to achieve a stronger immune response. Neuraminidase antigens change more slowly than hemagglutinin, the major antigen of flu pathogens. Such vaccines with antigen combinations may have a long and broad effect. Incidentally, influenza drugs such as oseltamivir inhibit viral neuraminidase.

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However, the use of such flu vaccines still has a long way to go, from animal testing to successful clinical studies on efficacy and tolerability. Research into the best influenza vaccines has been going on for decades. However, so far there has been no real improvement compared to conventional vaccines.

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