But why is there no universal vaccine as there is with other diseases? To understand this, you have to know how influenza viruses are structured. Science journalist Joachim Budde describes the appearance of the virus as a ball full of broccoli in a Deutschlandfunk report on universal flu vaccination and a comparison could hardly be more accurate. Broccoli is actually a protein and is known as hemagglutinin. Most flu vaccines encourage the immune system to attack the head so it can recognize and destroy the viruses on it. But it is precisely in the broccoli head that the viruses change: sometimes a small rose breaks out and a new one grows. The somewhat hidden neck section of the virus, on the other hand, is much more stable – basically the stem of broccoli.
The attack on the neck
After decades of research, the team led by virologists Florian Krammer and Peter Palese from the Icahn School of Medicine at Mount Sinai in New York found out how they can get the immune system to act against this neck of the protein. Because it is very similar with the flu strains, but our immune system, especially in younger people, doesn’t really care. However, the research team found antibodies that attack the neck in old people.
In a sense, the researchers wanted to train the immune system to focus on the neck. To do this, they have developed a technology that they call “reverse genetics” – something like reverse genetics to recreate viruses in the laboratory. About ten years ago they were able to recreate the 1918 Spanish flu virus. The universal vaccine is now based on this virus.
To put it simply, the team built a hemagglutinin chimera: They simply placed different heads of strains of bird flu on the neck and showed the immune system of test subjects one after the other – for example the neck of hemagglutinin variant 1 (H1) with the head of H8. The immune system has usually already seen the H1 neck, but antibodies against it are rare, according to the researchers. But if you now administer the chimeric hemagglutinin with the rather exotic H8 head, the immune system remembers the H1 neck and acts more strongly. This can then be repeated with a construct made up of an H1 neck and another head in order to intensify the effect.
Study shows broad and sustained immunity
After this theory had been shown to be effective in practice on animal models, the team started a clinical phase I study. The goal was a so-called “proof of concept” – so to speak, the proof that it also works in humans. And that is exactly what the researchers have now been able to successfully demonstrate. During the treatment with the chimeric protein, they were able to observe an increase in antibodies against the throat – so clearly that the virologist Krammer was able to conclude from the analysis of the first interim results:
The vaccine elicited a broad antibody response, and cross-reacted not only with the currently circulating human influenza viruses, but also with influenza subtypes of birds and bats.
In the randomized and placebo-controlled clinical phase I study, the researchers administered their vaccine candidates to young adults aged 18 to 39 years. They were divided into five groups and received their vaccinations three months apart. The result: The vaccination has proven to be safe and has led to a “broad, strong, permanent and functional immune response” against the stem of hemagglutinin.
The results suggest that chimeric hemagglutinins can be developed as universal vaccines that provide extensive protection against influenza viruses.
The vaccination was found to be safe and resulted in a broad, strong, sustained, and functional immune response against the conserved, immune-subdominant stem of hemagglutinin. The study has been published in the journal Nature.
The research team found that the antibody level remained at a consistently high level for months. It remains to be seen, however, whether the HA stalk antibody triggered by vaccination provides the same protection as the antibodies triggered by a natural infection. And yet the team concludes in summary: A vaccine made from chimeric hemagglutinin “can provide protection against all seasonal, zoonotic and emerging pandemic influenza viruses.” But it will take a few years of further research before such a universal flu vaccine can hit the market.