On the way in which to combating the flu: Immunological modeling brings us nearer to common flu vaccination
At a time when the world grapples with fears about how seasonal flu will complicate the Covid-19 pandemic, reports of a significant evolution in universal influenza vaccine efforts raise hope. The influenza virus is known to be difficult to vaccinate because different strains mutate at different rates. In fact, flu vaccines have shown a maximum effectiveness of ~ 60% in the best times of the year, while in the worst, the effectiveness was only 10 to 20%. This has resulted in public confidence in the vaccine being shaky. Factor in the 2-5 million severe influenza cases per year – and over half a million deaths (Indian and American researchers estimate in a study that a fifth of these deaths occur in India) – and the disease, even without Covid-19. poses a serious global public health problem.
To that end, researchers at MIT and the Ragon Institute of MIT, Massachusetts General Hospital, and Harvard University modeling a secular immunological pathway are a major step forward. Most flu vaccines have inactivated virus particles that express a surface protein (including such proteins) called hemagglutinin (HA). The human immune system mainly targets the head of the HA, which mutates pretty quickly. MIT-Ragon research shows that the surface geometry of the virus could induce head immunodominance (the front lining of this protein segment in the virus's fight against the immune system) compared to the stem part of HA which rarely mutates. On paper, the immune response to HA strains should produce the "largely neutralizing antibodies (bnABs)" that any influenza strain can take up. However, the clustering of HA heads and the geometry of the virus make it difficult for the immune system to reach the HA strain. Thus, the immune system's response to HA strains remains a competitive disadvantage versus that against HA heads in the maturation process of antibody affinity – which determines which antibodies dominate the immune response.
Using a nanoparticle vaccine developed at the National Institutes of Health to transport HA stem proteins closer together, MIT-Ragon researchers showed that it was possible to generate an HA stem antibody response . This was shown in mice designed to simulate a human immune response to the flu virus. The researchers also showed that using strain HA protein from a strain of virus that was similar but not identical to a strain the vaccine was exposed to before it induced a stronger immune response. Research is bringing the world closer to a universal flu vaccine, a very encouraging development in this day and age.
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