New research from Oregon Health & Science University reveals a promising approach to developing a universal vaccine againstinfluencea so-called “one-and-done” vaccine that confers lifetime immunity against an evolving virus.
A universal flu vaccine
The study, published in the journal Nature Communicationshas tested a vaccine platform developed by OHSU against the virus most likely to cause the next pandemic.
The researchers reported that the vaccine generated a robust immune response in nonhuman primates exposed to the H5N1 avian influenza virus. But the vaccine was not based on the contemporary H5N1 virus; instead, the primates were inoculated against the 1918 influenza virus that killed millions of people worldwide.
“It’s exciting because in most cases, this kind of basic science research advances science very gradually; in 20 years, it could be something,” said senior author Jonah Sacha, Ph.D., professor and chief of the Division of Pathobiology at the Oregon National Primate Research Center at OHSU. “This could actually be a vaccine in five years or less.”
Researchers have reported that six of 11 nonhuman primates vaccinated against a century-old virus, the 1918 flu, survived exposure to one of the world’s deadliest viruses today, H5N1. In contrast, a control group of six unvaccinated primates exposed to H5N1 died from the disease.
Sacha said he believes the platform could “absolutely” be useful against other mutant viruses, including SARS-CoV-2.
“It’s a very feasible approach,” he said. “For viruses with pandemic potential, it’s critical to have something like this. We decided to test influenza, but we don’t know what happens next.”
A senior coauthor from the University of Pittsburgh agrees.
“If a deadly virus like H5N1 were to infect a human and trigger a pandemic, we need to rapidly validate and distribute a new vaccine,” said co-corresponding author Douglas Reed, Ph.D., associate professor of immunology at the University of Pittsburgh’s Center for Vaccine Research.
This approach leverages a vaccine platform previously developed by OHSU scientists to fight HIV and tuberculosis, and which is already in use in an HIV clinical trial.
The method involves inserting small pieces of the target pathogen into the common herpes virus cytomegalovirus, or CMV, which infects most people at some point in their lives and typically produces mild or no symptoms. The virus acts as a specially engineered vector to induce an immune response from the body’s own T cells.
This approach differs from common vaccines, including existing influenza vaccines, which are designed to induce an antibody response that targets the most recently evolved version of the virus, characterized by the arrangement of proteins covering its outer surface.
“The problem with influenza is that it’s not one virus,” Sacha said. “Like SARS-CoV-2, it’s always evolving the next variant, and we’re always chasing where the virus was, not where it’s going to be.”
Spike proteins on the outside of the virus evolve to evade antibodies. In the case of influenza, vaccines are regularly updated using a better estimate of when the virus will evolve next. Sometimes it is accurate, sometimes less so.
In contrast, a specific type of T cell in the lungs, known as a memory effector T cell, targets the virus’s internal structural proteins, rather than its ever-changing outer shell. This internal structure doesn’t change much over time, presenting a stationary target for T cells to seek out and destroy any cells infected with an old or newly evolved flu virus.
To test their T-cell theory, the researchers designed a CMV-based vaccine using the 1918 influenza virus as a model. Working inside a highly secure Biosafety Level 3 laboratory at the University of Pittsburgh, they exposed vaccinated nonhuman primates to small aerosol particles containing the H5N1 avian influenza virus, a particularly serious virus currently circulating among dairy cows in the United States.
Remarkably, six of the 11 vaccinated primates survived the exposure, despite the virus having evolved over a century.
“It worked because the internal protein of the virus was so well conserved,” Sacha said. “So much so that even after almost 100 years of evolution, the virus can’t change those critical parts of itself.”
The study raises the chances of developing a protective vaccine against H5N1 in humans.
“Inhaling the aerosolized H5N1 influenza virus triggers 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 viral models, the new study suggests that CMV vaccines may be able to generate an effective and long-lasting immune response against a broad range of new variants.
“I think this means that within five to 10 years it will be possible to make a single dose against influenza,” Sacha said.
The same CMV platform developed by OHSU researchers has moved into clinical trials to protect against HIV, and a recent publication by those scientists suggests it may even be useful for targeting specific tumor cells. The HIV clinical trial is being led by Vir Biotechnology, which has licensed the vaccine platform from OHSU.
Sacha believes this development is the latest example of rapid progress in medical research aimed at curing or preventing disease.
“This is a huge sea change in our lifetime,” Sacha said. “There’s no doubt that we’re on the cusp of the next generation of how we deal with infectious disease.”
In addition to OHSU, research institutions involved in the study include the Tulane National Primate Research Center, the University of Pittsburgh, the University of Washington, and the Washington National Primate Research Center at the UW.
Goal: Universal protection against influenza
Dr. Hillary Vanderven, an immunology and infectious disease researcher and university professor, is racing against time with experts at the World Health Organization (WHO), who say the next influenza pandemic is a question of when, not if.
Working in JCU’s containment labs at the Australian Institute of Tropical Health and Medicine, where he tests flu antibodies, Dr Vanderven is determined to find a way to reduce the number of people who become seriously ill and die from flu.
“My research is focused on a dual goal: preventing people from getting sick from the flu and reducing the number of deaths through new treatments,” said Dr. Vanderven.
According to the WHO, seasonal influenza currently infects one billion people each year, including 3-5 million severe cases, and causes between 290,000 and 650,000 respiratory deaths.
When Dr. Vanderven is not busy teaching future biomedical science and molecular biology experts, supervising her doctoral students, or writing grant proposals, she focuses on her work in the lab.
Dr. Vanderven said working with new antibody-based therapies means looking closely at people’s different responses and asking why some people die from the flu while others don’t, and what we can learn from understanding what separates the two groups.
“There are specific antibodies that prevent people from dying because they help eliminate cells infected by the virus and perform other positive functions that are often ignored.”
Dr. Vanderven said she is looking for antibodies common to all strains of the influenza A virus, including seasonal, avian and swine variants.
“All influenza viruses have a spike protein called hemagglutinin, but within the virus there are other proteins that create a different type of immune response, and I think this has the potential to work with our existing vaccines and treatments, making them universally protective rather than strain-specific,” said Dr. Vanderven.
“For example, in America there is an outbreak of H5N1 avian influenza in cattle, so it should mutate and be transmitted from human to human. Our current seasonal vaccine will not cover this highly pathogenic (contagious) virus very well, so I would like to solve this problem and develop a universal vaccine that could protect against those viruses and allow for a rapid response to any emerging pandemic threat.”
Dr. Vanderven said not to panic because H5N1 could turn into a pandemic, but to keep an eye on the issue.
“There is a global lens on the occurrence of H5N1 cases in both animals and people, including here in Australia. People can be reassured that experts are constantly monitoring the genome of the virus to see what mutations are occurring and, unlike COVID, if it becomes a thing, we will have a heads-up,” Dr Vanderven said.
“We now know what to do and have more time to control a pandemic, if and when it happens. The important thing is, if a new flu vaccine is released to protect us more broadly against influenza or a specific virus like H5N1, then get it.”
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