As 2020 draws near to a close, it’s quite clear that the world was not ready for a pandemic — but hopefully, we will avert those that may follow. Influenza viruses have been responsible for many pandemics in the past, including the devastating 1918 Spanish flu that killed 50 million people worldwide. But a universal flu vaccine developed by researchers at Mount Sinai Hospital could stop a future influenza outbreak dead in its tracks before it gets the chance to develop into a pandemic.
There are quite a few strains of influenza circulating among people that cause seasonal flu, which is responsible for about 650,000 deaths every year globally. In order to prevent infection, people can get vaccinated but the problem is that there are not only different flu viruses circulating, but viruses can also mutate. If antibodies from a previous infection or vaccine meet a virus whose surface structure they don’t recognize, then those receptors don’t match and they cannot block it.
This is why we have to take a flu vaccine every year — and they’re not perfect. These vaccines contain three or four strains of the influenza virus, which public health experts predict will be circulating in the subsequent season. The problem is that sometimes these predictions don’t match the reality in the field, with different strains actually circulating among the population.
For years, scientists have been working on a universal vaccine that would both offer protection against multiple known strains of influenza and prime the body against new outbreaks. Of course, that’s easier said than done, but a vaccine developed at Mount Sinai Hospital in New York City may be the most promising one so far.
The chimeric hemagglutinin (HA)-based vaccine targets different parts of the hemagglutinin protein, the major surface glycoprotein of the influenza virus that binds to host cell receptors.
“An influenza virus vaccine that results in broad immunity would likely protect against any emerging influenza virus subtype or strain and would significantly enhance our pandemic preparedness, avoiding future problems with influenza pandemics as we see them now with COVID-19” says Florian Krammer, Professor of microbiology at the Icahn School of Medicine at Mount Sinai, and corresponding author of the study.
“Our chimeric hemagglutinin vaccine is a major advance over conventional vaccines which are often mismatched to the circulating strains of virus, impacting their effectiveness. In addition, revaccinating individuals annually is a huge and expensive undertaking.”
Conventional vaccines produce neutralizing antibodies by targeting a part of the hemagglutinin, known as the globular head domain. The problem is that mutations help the virus escape neutralization through a process known as “antigenic drift”, according to Peter Palese, professor of microbiology and chair of the Department of Microbiology at Icahn School of Medicine at Mount Sinai, and co-author of the study.
“This genetic change, or shift, in the virus results in immunity to only specific strains of the influenza virus, requiring frequent re-formulation and re-administration of seasonal vaccines. Our chimeric HA vaccine, by contrast, is directed at the proximal part of the HA protein — the stalk domain — which has been shown to broadly neutralize diverse influenza virus strains in both animal models and humans,” he added.
Such a vaccine not only offers broad protection but is also multifunctional, in the sense that the antibodies it induces can neutralize many kinds of influenza viruses.
For countries that lack an advanced medical infrastructure and the resources to vaccinate their population every year, a universal vaccine would be extremely appealing. Most importantly, as this pandemic has shown, we need robust tools at our disposal in order to nip potential devastating outbreaks in the bud.
Of course, safety is first. In a phase 1 clinical trial that involved 65 participants in the United States, the researchers found that the vaccine produced a strong immune response that was still viable 18 months after vaccination.
“This phase of our clinical work significantly advances our understanding of the immune response in terms of its longevity,” said Dr. Krammer, “and leaves us greatly encouraged about future progress for this potentially breakthrough vaccine.”
The findings appeared in the journal Nature Medicine.