New Hope for Flu Prevention
By OREGON HEALTH & SCIENCE UNIVERSITY
The study, published 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.
Finding a stationary target
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 in 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.”
Reference: “Cytomegalovirus vaccine vector-induced
effector memory CD4 + T cells protect cynomolgus macaques from lethal
aerosolized heterologous avian influenza challenge” by Daniel Malouli,
Meenakshi Tiwary, Roxanne M. Gilbride, David W. Morrow, Colette M. Hughes,
Andrea Selseth, Toni Penney, Priscila Castanha, Megan Wallace, Yulia Yeung,
Morgan Midgett, Connor Williams, Jason Reed, Yun Yu, Lina Gao, Gabin Yun, Luke
Treaster, Amanda Laughlin, Jeneveve Lundy, Jennifer Tisoncik-Go, Leanne S.
Whitmore, Pyone P. Aye, Faith Schiro, Jason P. Dufour, Courtney R. Papen, Husam
Taher, Louis J. Picker, Klaus Früh, Michael Gale Jr, Nicholas J. Maness, Scott
G. Hansen, Simon Barratt-Boyes, Douglas S. Reed and Jonah B. Sacha, 19 July
2024, Nature Communications.
DOI: 10.1038/s41467-024-50345-6
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.
Disclosures: OHSU and OHSU faculty involved in this
research, including Jonah Sacha, Ph.D., have a significant financial interest
in VIR Biotechnology Inc., a company that may have a commercial interest in the
results of this research and technology.
The research was supported by the Bill & Melinda
Gates Foundation Grand Challenges grant awards OPP1213553 and National
Institute of Allergy And Infectious Diseases of the National Institutes of Health award R01AI40888; with
support from the Office of the Director of the National Institutes of Health
award P51OD011092 to the Oregon National Primate Research Center at OHSU. The
findings and conclusions contained within are those of the authors and do not
necessarily reflect positions or policies of the Bill & Melinda Gates
Foundation or the National Institutes of Health.
