Even after decades of research and expansive global vaccination strategies, seasonal influenza still kills hundreds of thousands of people every year. The virus’s ability to mutate and evade our vaccines means we are constantly chasing the latest strains circulating in the population.
Current flu vaccines are designed to train the immune system to recognize a protein on the surface of the influenza virus called hemagglutinin (HA). The unique fingerprint on the head of these proteins is what our current flu vaccines aim for, but these protein heads are rapid mutators, which is why flu vaccines need to be reformulated every year.
Mutating much less often is a different part of the HA protein, referred to as the stalk. This section of the protein does not vary from one flu subtype to another, meaning it is a perfect target for a universal flu vaccine.
“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,” says co-author on the new research Peter Palase, explaining how this new type or flu vaccine stands apart from previous technologies. “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.”
Several kinds of stalk-targeting universal flu vaccines are currently in various stages of development. One method utilizes mRNA technology to help the immune system recognize HA stalks, while another technique uses nanoparticles to induce effective protection. And while several first-phase human trials are underway testing the safety and efficacy of these different stalk-based flu vaccines, until now none have reported any results.
A newly published study in the journal Nature Medicine is the first to report successful results of a Phase 1 trial testing a universal flu vaccine targeting HA stalks. The Phase 1 trial, led by researchers from the Icahn School of Medicine at Mount Sinai, found this experimental vaccine to be both safe and effective at generating a long-term immune response in a small number of healthy adults.
Promisingly, the study found the HA stalk antibodies elicited by the vaccine persisted for at least 18 months after the trial had been completed. This suggests the vaccine offers the potential for long-lasting protection against all strains of influenza, removing the need for annual vaccinations.
The researchers are cautious to stress this is only a Phase 1 human trial, and it is not designed to evaluate whether the vaccine protects against disease or infection. Instead, these preliminary studies focus on safety and initial immune response. But from this perspective the data so far is significantly promising, offering up all the signs to support further development of a universal influenza vaccine.
“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,” adds corresponding author on the new study Florian Krammer. “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.”
The new study was published in the journal Nature Medicine.
Source: Mount Sinai
