Vaccines to reduce pollen allergy, low-molecular-weight LDL cholesterol, and a universal flu vaccine – in the past two years, the field of vaccines has made great progress and is now bearing fruit.
Scientists are getting closer to a vaccine not so much universal as it blocks all strains of the influenza A virus. This time, a team of researchers from Georgia State University, led by Dr. Lei Deng, set about creating a vaccine that would block different variants of the A virus, thereby preventing the “Achilles’ heel” of vaccines – a mismatch with the virus that causes the disease. Vaccine updates for the fall / winter season are made in the spring, and even if virologists make no mistake about the strain of the virus, there is time for a new strain to emerge for which the vaccine will be less effective. In 2009, the H1N1 pandemic virus caused 200 deaths. worldwide deaths in the first 12 months. In turn, reduced vaccine activity was observed in the 2014/2015 and 2016/2017 flu seasons. A universal vaccine would offer broader antiviral protection, lifting restrictions on vaccines for seasonal strains of the virus.
Seasonal flu vaccines necessarily target the most important virus surface protein, haemagglutinin (HA). The virus produces antibodies to prevent the part of the molecule responsible for adhering to cell receptors from being deactivated. This part is different for each virus and varies over time – as it mutates – which makes it necessary to change vaccines. Meanwhile, the researchers concluded that another HA fragment could be blocked that did not mutate as often, thereby blocking all virus activity.
“Vaccination is the most effective way to prevent death from influenza, but the virus mutates very quickly and post-season vaccination is necessary. We wanted to create a vaccine that would eliminate annual vaccinations. Vaccination would be necessary if the type of virus was changed, »says researcher from the team, Dr. Bao-Zhong Wang. Researchers decided to block the virus from penetrating the lipid envelope, i.e. penetrating into the cell. For this purpose, a large fragment of the haemagglutinin chain, which is not highly variable, is “packed” in a protein nanoparticle shell. It is two-tier. It protects the haemagglutinin fragment from degradation. The immune system can take up this protein and recognize it. It is then easier to identify different strains within the A / HxNx virus type, i.e. all strains of influenza A. To prove the effectiveness of the vaccine, mice were vaccinated twice with doses and then exposed to different influenza viruses: H1N1, H3N2, H5N1 and H7N9. The vaccine saved the animals from death and significantly reduced the amount of virus that entered the lungs.
Vaccine trials have now begun in ferrets, which are a model of human flu, because the respiratory and circulatory systems are similar. As noted by the researcher, Dr. Lei Deng, seasonal flu vaccines activate an immune response, mainly in the surface part of the HA molecule, which is variant variable and therefore need to be vaccinated every year, and the new vaccine avoids this problem. Clinical tests will now be needed, including also on volunteers who will test the effectiveness of the new vaccine under the conditions of the flu season.
Pollen vaccine
In turn, the team from MedUniWien and the Austrian company Biomay AG, led by Dr. Rudolf Venta from the Christian Doppler Laboratory for Allergy Research and Dr. Verena Niederberger-Leppin from MedUni Vienna, focused on the common allergy to grass pollen. It is one of the most common allergies – 400 million people worldwide suffer from it in various forms and degrees. In the light form, it causes a runny nose, in the more severe form – runny nose and cough, and even breathing problems. The team developed and implemented a synthetic BM32 vaccine that completely eliminates breathing problems and reduces all other symptoms by 25%, which is a significant improvement. Unfortunately, so far you have to use it often – in the first year to quarter, and in the second as booster doses. It has very few side effects, mainly on the part of the digestive system, which means that the therapy in this way is simpler and has less impact on the body than the therapy with traditional antiallergic drugs.
It is quite a complicated vaccine. Peptide reactive B cells were isolated by innovative technology from the allergen. The peptide was modified so that it lost the ability to bind to specific IgE antibodies, which appear only in allergies. It serves as a “transporter” of proteins for the necessary activation of T lymphocytes, as Dr. Valenta explains, this process can be repeated continuously and the vaccine does not lose its properties and quality and remains safe. Scientists say allergy symptoms will continue to decrease if the vaccine is used for more than two years – during this period, tests were carried out and the respiratory symptoms were reduced and others were reduced by 25%. According to Dr. Verena Niederberger-Leppin, the more severe the form of allergy, the greater the relief after vaccination. You can also use the vaccine preventively. It is currently being tested in 11 European countries in 240 centers dealing with allergy therapy. The production of the new vaccine is to be carried out by Biomay AG. Market entry is expected after all tests are completed in 2021.
Vaccination will reduce LDL levels
Currently, clinical trials are ending for an innovative vaccine that reduces LDL cholesterol and reduces the deposition of cholesterol in the blood vessels, and thus does not drastically narrow the lumen of the blood vessels.
High LDL is due to either genetic causes or a poor diet or lifestyle. People with this defect are at risk of cardiovascular disease, arteriosclerosis, somatic infections, and subsequent strokes or strokes, leading to premature death. Although the drugs used in therapy – statins – are quite well tolerated, they have various side effects, including cause liver disorders. You also need to download them daily. They usually contain monoclonal antibodies directed at the enzyme PCSK9 (Proprotein covertase subtilisin / kexin type 9), which counteracts the reduction of low-density lipoprotein cholesterol, or LDL. These counteracts work for a short time, which means that they need to be used often, which, apart from the inconvenience, significantly increases the costs of therapy.
Meanwhile, a team from MedUniWien and AFFiRis has developed an innovative AT04A vaccine. When administered subcutaneously in an in vivo fat-fed mice diet equivalent to the current Western European diet in humans, the vaccine reduced cholesterol by 53%, and reduced arteriosclerotic damage to blood vessels by 64%. and markers of inflammation of blood vessels decreased by 21-28 percent compared to unvaccinated control mice but on the same diet. In addition, the level of antibodies fluctuated only slightly from the beginning to the end of the study, within the assumed limits. According to Dr. Günther Staffler, head of technology at AFFiRis, the AT04A vaccine can induce antibodies specifically targeting the PCSK9 enzyme. They stay in the blood for a very long time; for in vivo testing, the entire testing period. PCSK9 is produced in the liver. It attaches to LDL cholesterol receptors, reducing the chance of it being released from the blood. The use of AT04A causes the production of antibodies that block the function of PCSK9 and the activity of LDL cholesterol receptors increases, which means that this cholesterol disappears from the blood faster. It is likely that this vaccine will be available in 2020.