Every year in autumn there is a fixed appointment for the most at-risk categories: the influenza vaccination campaign. This is because the viruses that cause influenza are subject to mutation, and vaccines are modified annually because they may not correspond to the most virulent strains of the season. So much so that a ‘coveted’ goal for many researchers is to be able to develop a universal vaccine capable of offering broad protection against serious infections, covering all viral strains and ideally for longer than a single season. A treacherous challenge that has not yet been won. But a study published this week in the ‘Journal of Virology’ suggests that perhaps we are getting closer to the finish line.
Researchers from the Cleveland Clinic’s Lerner Research Institute have presented the results obtained with their candidate Universal flu vaccine, tested on animal models. Administered as a spray, intranasally, this vaccine that incorporates proteins from eight influenza strains, elicited a strong immune response in model mice, and provided protection after viral exposure. Blood tests showed that 4 weeks after administration, the animals had developed antibodies and were protected from developing infection when they were exposed to the pathogen. The new work builds on earlier, equally promising preclinical studies conducted by the same group led by Ted M. Ross, director of global vaccine development at the Cleveland Clinic.
There Experts hope to start clinical trials on humans within 1-3 yearsexplains virologist Naoko Uno, who led the new study. “We want to make sure our vaccine can cover multiple seasons, not just one, and protect against all strains affecting humans.“. Scientists have identified four types of influenza viruses, but two of them, influenza A and influenza B, pose the greatest risk to humans. Seasonal flu vaccines include proteins from three or four circulating subtypes of those viruses. But because the virus mutates so rapidly, choosing which ingredients to include in vaccines becomes something of a guessing game.
How it works
Researchers in Ross’s lab designed their new vaccine candidate using a methodology called Cobra (Computationally Optimized Broadly Reactive Antigens). They started by downloading thousands of genetic sequences of pathogenic influenza strains, spanning multiple seasons, from an online database. They then digitally analyzed the sequences to identify which amino acids, the building blocks of proteins, were conserved across viruses and seasons. The researchers then identified groups of proteins for different subtypes. To develop a more broad-based vaccine, Naoko Uno says, the team identified eight proteins associated with a sustained immune response. “We were able to narrow that down to say these are the best ones to span multiple seasons and elicit a broadly reactive antibody response,” Uno says. “It’s like creating a greatest hits album.”
Those big hits included proteins from H1 and H3 influenza viruses, Uno said, but also proteins from H2, H5 and H7 viruses, which are strains that most people don’t have antibodies against. Some of these have pandemic potential, Uno said, citing recent developments in H5N1 avian influenza. “We’ve shown that our H5 vaccine covers many different clades,” she said. Ross is now directing her team’s efforts to advance testing of the candidate in the United States, and Uno is collaborating with researchers in India and the European Union on an international effort. The Cobra methodology, the team said, isn’t limited to finding and assembling recombinant proteins for influenza. It could be used to analyze mRNA or other biomolecules, or explored to develop vaccines for viral diseases like dengue. “It can be used in many viruses.”
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