A new flu vaccine candidate combines proteins from 8 different influenza strains.
While annual flu vaccinations help protect against severe cases, their effectiveness can fluctuate, and they may not always correspond to the most aggressive strains for that season. The concept of a universal flu vaccine that would provide protection against all variants, ideally lasting longer than a single season, remains a challenging goal.
Recent research featured in the Journal of Virology indicates that progress is being made in this area. Scientists from Cleveland Clinic’s Lerner Research Institute have announced that their universal flu vaccine candidate, tested in animal models, triggered a robust immune response and shielded against serious infection after exposure to the virus. This recent study builds on earlier, promising experiments conducted on mice by the same research team led by Ted M. Ross, Ph.D., who oversees Global Vaccine Development at Cleveland Clinic.
According to virologist Naoko Uno, Ph.D., who led this new research, the team aims to begin human clinical trials within the next 1-3 years. “We are focused on creating a vaccine that can provide protection across multiple flu seasons, not just one, and against all strains that affect humans,” she explained.
There are 4 known types of influenza viruses, but the most considerable threats to humans come from Influenza A and Influenza B. Current seasonal flu vaccines typically contain proteins from 3 or 4 subtypes of these viruses, such as H1N1, H3N2, and IBV. However, the rapid mutation of the virus makes it challenging to predict which strains will be most dangerous, turning the selection of vaccine components into a guessing game.
To tackle this, researchers in Ross’ laboratory developed their new vaccine using a technique called COBRA, which stands for Computationally Optimized Broadly Reactive Antigens. They started by accessing thousands of genetic sequences of virulent influenza strains from an online database, spanning different seasons. They then digitally analyzed these sequences to pinpoint conserved amino acids—the essential components of proteins—across various viruses and over time.
The researchers identified groups of proteins for various subtypes. In order to create a more effective vaccine, Uno mentioned that the team selected 8 proteins from previous studies known to generate a lasting immune response. “We narrowed it down to determine which proteins are the most effective across multiple seasons and stimulate a broadly reactive antibody response,” she stated. “It’s akin to assembling a ‘greatest hits’ album; we want to include only the top performers in the vaccine.”
These top proteins included selections from both H1 and H3 strains of influenza, but also encompassed proteins from H2, H5, and H7 viruses, which many individuals lack antibodies against. Some of these have the potential to cause pandemics, as pointed out by Uno. Historical outbreaks of bird flu, such as H5N1, have resulted in significant human mortality, and as of March 2024, this virus was detected in dairy cows in Texas. Since then, four individuals who work with these cattle have been diagnosed, and the virus has spread across numerous herds in various states, as well as to other species like sea lions, birds, cats, and alpacas.
“Our H5 vaccine has demonstrated its effectiveness against many different clades,” UNO stated.
In their latest study, the Cleveland Clinic researchers administered the vaccine candidate intranasally. Blood tests revealed that four weeks later, the animals had developed antibodies against the virus, and they showed protection against infection when exposed to the pathogen.
Currently, Ross is spearheading efforts in the U.S. to advance testing of the vaccine candidate, while Uno collaborates with scientists in India and the European Union for an international initiative.
Uno emphasized that the COBRA technique is not confined to designing recombinant proteins for influenza; it could also be applied to analyze mRNA or other biomolecules. Furthermore, it may be used to develop vaccines for viral diseases such as dengue. “This approach has far-reaching applications across various viruses,” she noted.
