Is a universal influenza vaccine on the horizon?
Researchers are developing a ‘one and done’ vaccine that will protect individuals against all influenza variants after only one vaccination.
A team led by researchers at Oregon Health & Science University (OHSU; OR, USA) have developed and tested a vaccine platform against an influenza variant thought most likely to cause the next pandemic. Not only does this platform demonstrate promising results against flu variants, but it also has the potential to apply to other viruses, a breakthrough that could change the infectious disease landscape of the future.
Viruses are ever evolving, making them difficult to target and keep up with. Many vaccines are designed to induce an antibody response, targeting the virus specifically depending on the arrangement of viral surface proteins. However, this approach always leaves us on the back foot: “The problem with influenza is that it’s not just one virus,” commented senior author Jonah Sacha (OHSU). “Like the SARS-CoV-2 virus, it’s always evolving the next variant and we’re always left to chase where the virus was, not where it’s going to be.”
The current study investigated how to get ahead of a virus’s variants, focusing on avian H5N1 influenza virus, which is the virus considered most likely to trigger the next pandemic. It is currently considered one of the deadliest viruses in the world and is circulating in US dairy cows.
New insights into influenza’s replication mechanism
Investigating influenza’s interactions with cellular proteins has led to an improved understanding of how it is able to jump between different types of hosts.
In the hopes of combatting avian H5N1 influenza virus and other potential variants, the researchers utilized a vaccine platform previously developed at OHSU to fight HIV and tuberculosis; the vaccine they designed for HIV is currently in clinical trials. The platform involves inserting fragments of target pathogens into cytomegalovirus, the common herpes virus that infects most people and produces mild symptoms. It differs from common vaccine design in that it induces an immune response from one’s own effector memory T cells, which targets the virus’s internal structural proteins, not its evolving membrane proteins.
The researchers designed their cytomegalovirus-based vaccine using the 1918 influenza virus as a template before vaccinating 11 nonhuman primates. In a secure biosafety level 3 lab, these primates were then exposed to small particle aerosols containing the avian H5N1 influenza virus. Six unvaccinated primates were similarly exposed as a control. Six of the vaccinated primates survived, while all 6 of the unvaccinated primates perished, indicating that the vaccine – although based on the 1918 virus – was able to mobilize the memory T cells against the internal structural proteins of the deadly H5N1 strain. The core of the 1918 virus was similar enough to the H5N1 virus to encode protection; Sacha remarked, “even after almost 100 years of evolution, the virus can’t change those critically important parts of itself.”
Co-senior author Simon Barratt-Boyes (University of Pittsburgh, PA, USA) explained: “Inhalation of aerosolized H5N1 influenza virus causes a cascade of events that can trigger respiratory failure. The immunity induced by the vaccine was sufficient to limit virus infection and lung damage, protecting the monkeys from this very serious infection.”
Their findings in primates have led many to wonder about the vaccine platform’s potential in humans. In future, following the synthesis of more recent flu virus templates, the researchers expect a universal influenza vaccine to exist for human vaccination, which could generate an effective, long-lasting T-cell response against a range of unknown variants.
