New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called “one and done” vaccine that confers lifetime immunity against an evolving virus.
The study, published today in the journal Nature Communications, tested an OHSU-developed vaccine platform against the virus considered most likely to trigger the next pandemic.
Researchers reported the vaccine generated a robust immune response in nonhuman primates that were exposed to the avian H5N1 influenza virus. But the vaccine wasn’t based on the contemporary H5N1 virus; instead, the primates were inoculated against the influenza virus of 1918 that killed millions of people worldwide.
“It’s exciting because in most cases, this kind of basic science research advances the science very gradually; in 20 years, it might become something,” said senior author Jonah Sacha, Ph.D., professor and chief of the Division of Pathobiology at OHSU’s Oregon National Primate Research Center. “This could actually become a vaccine in five years or less.”
Researchers reported that six of 11 nonhuman primates inoculated against the virus that circulated a century ago—the 1918 flu—survived exposure to one of the deadliest viruses in the world today, H5N1. In contrast, a control group of six unvaccinated primates exposed to the H5N1 virus succumbed to the disease.
Sacha said he believes the platform “absolutely” could be useful against other mutating viruses, including SARS-CoV-2.
“It’s a very viable approach,” he said. “For viruses of pandemic potential, it’s critical to have something like this. We set out to test influenza, but we don’t know what’s going to come next.”
A senior co-author from the University of Pittsburgh concurred.
“Should a deadly virus such as H5N1 infect a human and ignite a pandemic, we need to quickly validate and deploy a new vaccine,” said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at the University of Pittsburgh Center for Vaccine Research.
This approach harnesses a vaccine platform previously developed by scientists at OHSU to fight HIV and tuberculosis, and in fact is already being used in a clinical trial against HIV.
The method involves inserting small pieces of target pathogens into the common herpes virus cytomegalovirus, or CMV, which infects most people in their lifetimes and typically produces mild or no symptoms. The virus acts as a vector specifically designed to induce an immune response from the body’s own T cells.
This approach differs from common vaccines—including the existing flu vaccines—which are designed to induce an antibody response that targets the most recent evolution of the virus, distinguished by the arrangement of proteins covering the exterior surface.
“The problem with influenza is that it’s not just one virus,” Sacha said. “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 spike proteins on the virus exterior surface evolve to elude antibodies. In the case of flu, vaccines are updated regularly using a best estimate of the next evolution of the virus. Sometimes it’s accurate, sometimes less so.
In contrast, a specific type of T cell in the lungs, known as effector memory T cell, targets the internal structural proteins of the virus, rather than its continually mutating outer envelope. This internal structure doesn’t change much over time—presenting a stationary target for T cells to search out and destroy any cells infected by an old or newly evolved influenza virus.
Success with a century-old template
To test their T cell theory, researchers designed a CMV-based vaccine using the 1918 influenza virus as a template. Working within a highly secure biosafety level 3 laboratory at the University of Pittsburgh, they exposed the vaccinated nonhuman primates to small particle aerosols containing the avian H5N1 influenza virus—an especially severe virus that is currently circulating among dairy cows in the United States.
Remarkably, six of the 11 vaccinated primates survived the exposure, despite the century-long period of virus evolution.
“It worked because the interior protein of the virus was so well preserved,” Sacha said. “So much so, that even after almost 100 years of evolution, the virus can’t change those critically important parts of itself.”
The study raises the potential for developing a protective vaccine against H5N1 in people.
“Inhalation of aerosolized H5N1 influenza virus causes a cascade of events that can trigger respiratory failure,” said co-senior author Simon Barratt-Boyes, Ph.D., professor of infectious diseases, microbiology and immunology at Pitt. “The immunity induced by the vaccine was sufficient to limit virus infection and lung damage, protecting the monkeys from this very serious infection.”
By synthesizing more up-to-date virus templates, the new study suggests CMV vaccines may be able to generate an effective, long-lasting immune response against a wide suite of new variants.
“I think it means within five to 10 years, a one-and-done shot for influenza is realistic,” Sacha said.
The same CMV platform developed by OHSU researchers has advanced to a clinical trial to protect against HIV, and a recent publication by those scientists suggests it may even be useful for targeting specific cancer cells. The HIV clinical trial is being led by Vir Biotechnology, which licensed the vaccine platform from OHSU.
Sacha sees the development as the latest in the rapid advance of medical research to treat or prevent disease.
“It’s a massive sea change within our lifetimes,” Sacha said. “There is no question we are on the cusp of the next generation of how we address infectious disease.”
In addition to OHSU, research institutions involved in the study included the Tulane National Primate Research Center, the University of Pittsburgh, the University of Washington, and the Washington National Primate Research Center at the UW.
More information: Cytomegalovirus vaccine vector-induced effector memory CD4+ T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza, Nature Communications (2024).
News
How bacteria trigger colon cancer
In a recent study published in Nature, scientists used murine models to investigate how certain bacteria, such as Escherichia coli strains that contain a polyketide synthase (pks) island encoding enzymes that produce colibactin genotoxin, could increase the [...]
Nanoparticles designed to trap and neutralise large amounts of SARS-CoV2
(Nanowerk News) Researchers from the IBB-UAB have developed a new class of nanostructures capable of trapping and neutralising large quantities of the SARS-CoV2 virus particles, both in liquid solutions and on the surface of [...]
Nanodiscs: What Are They and How Are They Shaping the Future of Medicine?
Nanodiscs are synthetic phospholipid particles with a distinct morphology and size that enhance their efficiency in drug delivery applications.1 First developed by Sligar et al. in the early 2000s, these model membrane systems measure around 10 [...]
New Discovery Reveals How Ovarian Cancer Starves Immune Cells
Researchers discovered that ovarian tumors hinder T cells’ energy supply by trapping a key protein, blocking lipid uptake. A new approach to reprogram T cells could enhance immunotherapy for aggressive cancers. Researchers at Weill Cornell [...]
Innovative Drug-Design Strategies to Overcome Antibacterial Resistance
Antibacterial resistance occurs when antibiotics fail to treat bacterial infections. This incidence is considered one of the top global health threats, stemming from the misuse or overuse of antibiotics in humans and animals.1 The [...]
Team introduces a cost-effective method to redesign search engines for AI
The internet search engine of the future will be powered by artificial intelligence. One can already choose from a host of AI-powered or AI-enhanced search engines—though their reliability often still leaves much to be [...]
Experiments demonstrate precise delivery of nanoparticles to lung
In recent years, bio-medical engineers have been developing promising techniques that could help diagnose diseases or precisely target specific regions inside the human body. Among these promising therapeutic strategies are methods that rely on [...]
What is Lassa fever? Everything to know about Ebola-like virus
Lassa fever has reached the US for the first time in a decade, in a case that has surprised health officials. The middle-aged patient in Iowa, who was not identified, died a 'short time' after being hospitalized [...]
Harvard Study Links Popular Plastic Ingredient to DNA Damage
Phthalate affects egg formation in C. elegans, resulting in abnormal chromosome numbers. A recent study conducted on roundworms has discovered that a common plastic ingredient can cause DNA strand breaks, leading to egg cells with an abnormal [...]
New research finds that subtle eye movements optimize vision
Our ability to see starts with the light-sensitive photoreceptor cells in our eyes. A specific region of the retina, termed fovea, is responsible for sharp vision. Here, the color-sensitive cone photoreceptors allow us to [...]
Scientists Were Wrong: Plants Absorb 31% More CO2 Than Previously Thought
New research shows plants absorb 31% more CO2 than previously estimated, raising the global GPP to 157 petagrams per year. Using carbonyl sulfide as a proxy for photosynthesis, this study highlights tropical rainforests’ critical role [...]
Doctors test first mRNA vaccine against norovirus
According to the Robert Koch Institute (RKI), the norovirus, which is widespread worldwide, is the cause of a large proportion of gastrointestinal infections. Those who catch the virus suffer from nausea, diarrhea and vomiting. [...]
Study reveals resistance of Pseudomonas aeruginosa to common cleaning agents
A new study reveals widespread resistance of a major bacterial pathogen to the active ingredients in cleaning agents commonly used in hospitals and homes. The American Chemical Society Infectious Diseases published the research, led [...]
AI’s Next Frontier: System 0 and the Future of Human Thought
“System 0” represents an emerging cognitive tool powered by AI that works alongside human intuition and analysis to enhance cognitive abilities. This new system promises to support complex decision-making and problem-solving but requires careful [...]
The Global Nanomedicine Market: Key Players and Emerging Technologies in Healthcare
This article provides an overview of the global nanomedicine market, highlighting key players, emerging technologies, and the challenges and opportunities that influence its growth and commercialization in the healthcare sector. Nanomedicines are nanotechnology-based drug products [...]
Scientists Have Discovered Toxic “Forever Chemicals” in Bottled Water
Scientists have found toxic PFAS in drinking water samples from around the world, with higher levels in tap water from China compared to the UK. Boiling water or using a filtration jug can reduce [...]