Towards conquering flu: Immunological modelling brings us closer to a universal flu shot

By: |
October 17, 2020 5:30 AM

To that end, researchers at MIT and the Ragon Institute of MIT, Massachusetts General Hospital and Harvard University modelling a secular immunological pathway is a significant step forward.

Thus, the immune system response to HA stems remains at a competitive disadvantage to that against HA heads in the antibody affinity maturation process—which determines, which antibodies will dominate the immune response. (Representative image)Thus, the immune system response to HA stems remains at a competitive disadvantage to that against HA heads in the antibody affinity maturation process—which determines, which antibodies will dominate the immune response. (Representative image)

At a time when the world is grappling with apprehensions over how seasonal flu will complicate the Covid-19 pandemic situation, reports of a significant development in the universal influenza vaccine efforts stir hope. The influenza virus is notoriously difficult to target for vaccination, given the different strains and how rapidly these mutate. Indeed, in the best seasons, flu vaccines have demonstrated a maximum of ~60% efficacy, while in the worst ones, the efficacy was as low as 10-20%. This has meant public faith on the vaccine is shaky. Factor in the 2-5 million severe influenza cases every year—and over half a million deaths (Indian and American researchers estimate in a study that a fifth of these deaths happen in India)—and the disease, even without Covid-19 around, presents a serious global public health concern.

To that end, researchers at MIT and the Ragon Institute of MIT, Massachusetts General Hospital and Harvard University modelling a secular immunological pathway is a significant step forward. Most flu vaccines have inactivated viral particles expressing a surface protein (among other such proteins) called haemagglutinin (HA). The human immune system primarily targets the head of the HA, which mutates quite rapidly. The MIT-Ragon research shows that the virus’s surface geometry could be giving the head immunodominance (front lining this segment of the protein in the virus’s fight against the immune system) compared to the stem part of HA that rarely mutates. On paper, the immune response to HA stems should produce the “broadly neutralising antibodies (bnABs)” that can take on any influenza strain. But, clustering of HA heads and the virus’s geometry make it difficult for the immune system to reach the HA stem. Thus, the immune system response to HA stems remains at a competitive disadvantage to that against HA heads in the antibody affinity maturation process—which determines, which antibodies will dominate the immune response.

Using a nanoparticle vaccine developed at the National Institutes of Health to carry HA stem proteins spaced out in a less dense manner, MIT News reports, the MIT-Ragon researchers showed that it was possible to generate an HA-stem antibody response. This was demonstrated in mice engineered to simulate a human immune response to the flu virus. The researchers also showed that using HA-stem protein from a viral strain that was similar to, but not the same as, a strain the vaccine subject has been exposed to before it induced a stronger immune response. The research puts the world closer to a universal flu vaccine, a very heartening development in the current times.

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