New findings indicate a potential breakthrough in the development of a universal influenza vaccine, described as a ‘one and done’ vaccine providing lifelong protection against a changing virus. The research focused on a vaccine platform tested against the virus predicted to be the likely cause of the next pandemic.
Fresh research led by Oregon Health & Science University showcases a promising strategy in creating a universal influenza vaccine that could confer lifelong immunity against an evolving virus.
The research, released today in the journal Nature Communications, examined a vaccine developed by OHSU against the virus considered the top candidate for causing the next pandemic.
Scientists found that the vaccine triggered a strong immune response in nonhuman primates exposed to the avian H5N1 influenza virus. Notably, the vaccine was not based on the current H5N1 virus; instead, the primates were immunized against the influenza virus from 1918, responsible for a significant global death toll.
Senior author Jonah Sacha, Ph.D., professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center, expressed enthusiasm about the accelerated progress of this research: “This could actually become a vaccine in five years or less,” he remarked.
The study revealed that out of 11 primates vaccinated against the 1918 flu strain, six survived exposure to the highly lethal H5N1 virus. In contrast, a control group of six unvaccinated primates succumbed to the disease when exposed to H5N1.
Sacha highlighted the potential of the platform to combat other mutating viruses, including SARS-CoV-2.
“It’s a very viable approach,” he emphasized. “For viruses with pandemic potential, having a solution like this is crucial. While our focus was on influenza, the future remains unpredictable.”
A senior co-author from the University of Pittsburgh shared the same sentiment.
“In the event of a deadly virus such as H5N1 infecting a human and causing a pandemic, it is essential to swiftly validate and deploy a new vaccine,” stated co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at the University of Pittsburgh’s Center for Vaccine Research.
Targeting a Stable Enemy
This novel approach utilizes a vaccine platform previously developed by OHSU scientists for combating HIV and tuberculosis, already undergoing a clinical trial for HIV.
The technique involves incorporating fragments of target pathogens into the common cytomegalovirus, or CMV, known to infect a majority of people without causing severe symptoms. This virus serves as a vector specifically engineered to stimulate an immune response from the body’s T cells.
Contrary to traditional vaccines, including current flu vaccines, designed to provoke an antibody response targeting the latest virus variants, this method varies.
Sacha explained the challenge posed by influenza’s continuous evolution: “Like the SARS-CoV-2 virus, it’s always evolving, and we’re left chasing where the virus has been, not where it’s headed.”
The exterior spike proteins of the virus evolve to evade antibodies. In the case of influenza, vaccines are regularly updated based on the projected evolution of the virus, a process prone to varied accuracy.
Conversely, a specific type of T cell in the lungs, known as effector memory T cell, targets the virus’s internal structural proteins rather than its ever-changing outer surface. This stable internal structure presents a consistent target for T cells to identify and eliminate any cells infected by an old or newly evolved influenza virus.
Success with a Time-Tested Model
To test their T cell theory, researchers developed a CMV-based vaccine modeled after the 1918 influenza virus. Within a highly secure biosafety level 3 lab at the University of Pittsburgh, they exposed vaccinated primates to aerosols containing the avian H5N1 influenza virus — a potent strain currently circulating amongst dairy cows in the U.S.
Surprisingly, six out of the 11 vaccinated primates survived the exposure, despite nearly a century of virus evolution.
“The success was due to the remarkably preserved internal protein of the virus,” Sacha noted. “Even after close to 100 years of evolution, the virus cannot alter these crucial components of itself.”
The study indicates the potential for developing a protective vaccine against H5N1 for humans.
“Inhaling aerosolized H5N1 virus sets off a series of events that can lead to respiratory failure,” mentioned co-senior author Simon Barratt-Boyes, Ph.D., professor of infectious diseases, microbiology, and immunology at Pitt. “The induced immunity effectively limited virus infection and lung damage, shielding the monkeys from this severe infection.”
By generating updated virus templates, the research proposes that CMV vaccines could elicit a durable, efficient immune response against a range of emerging variants.
“I believe a one-time influenza shot could become a reality within five to ten years,” Sacha projected.
The same CMV platform developed by OHSU researchers is undergoing a clinical trial to combat HIV, and recent publications suggest a potential application in targeting specific cancer cells. The HIV trial is overseen by Vir Biotechnology, which holds the license for the vaccine platform from OHSU.
Sacha views this endeavor as part of the swift progress in medical research for disease prevention and treatment.
“We are on the brink of a new era in addressing infectious diseases,” Sacha remarked. “It represents a significant shift in our lifetime.”
Aside from OHSU, the study involved research institutions such as the Tulane National Primate Research Center, the University of Pittsburgh, the University of Washington, and the Washington National Primate Research Center at the UW.