This Vaccine Stops Bird Flu Before It Reaches the Lungs
By WashU Medicine
more than 70 people in the U.S. have been
infected, including two deaths. Because the virus continues to circulate widely
among animals, scientists warn that it has ongoing opportunities to adapt in
ways that could allow it to spread more easily between people, raising fears of
a future pandemic.
A Nasal Vaccine Designed to Stop Infection Early
To reduce that risk, researchers at Washington University
School of Medicine in St. Louis developed a nasal spray vaccine aimed at
stopping the virus at its point of entry. When tested in hamsters and mice, the
vaccine triggered strong immune responses and successfully prevented infection
after exposure to H5N1.
One major concern with bird flu vaccines is that immunity
from previous seasonal flu infections or vaccinations could weaken their
effectiveness. The research team addressed this issue directly and found that
their nasal vaccine remained highly protective even in animals with prior flu
immunity.
The findings were published today (January 30) in Cell
Reports Medicine.
“This particular version of bird flu has been around for some time, but the unique and totally unexpected event where it jumped across species into dairy cows in the United States was a clear sign that we should prepare for the event that a pandemic may occur,” said Jacco Boon, PhD, a professor in the WashU Medicine John T. Milliken Department of Medicine and co-senior author of the study.
“Our vaccine to the nose and upper
airway — not the shot-in-the-arm vaccine people are used to — can protect
against upper respiratory infection as well as severe disease. This could
provide better protection against transmission because it protects against
infection in the first place.”
Building a Better Bird Flu Vaccine
While a bird flu vaccine already exists, it was designed
using older strains of the virus, may not work well against current variants,
and is not widely available. To develop a more effective option, Boon and his
colleagues built on nasal vaccine technology previously created at WashU
Medicine by co-authors Michael S. Diamond, MD, PhD, the Herbert S. Gasser
Professor of Medicine, and David T. Curiel, MD, PhD, a professor of radiation
oncology. A COVID-19 vaccine based on this same platform has been in
use in India since 2022 and received approval for clinical testing in the U.S.
last year.
Effective vaccines depend on the immune system’s ability to
recognize a virus quickly and accurately. For the H5N1 vaccine, Boon and
co-author Eva-Maria Strauch, PhD, an associate professor of medicine
specializing in antivirals and protein design, selected proteins from strains
of bird flu that have infected humans. Using shared features from these viral
proteins, they engineered an optimized antigen, the part of the virus that
triggers an immune response. This antigen was then placed into a harmless, non-replicating
adenovirus, which serves as the delivery vehicle for the vaccine. The overall
design closely resembles the team’s COVID-19 nasal vaccine approach.
Strong Protection in Animal Tests
In laboratory testing, the nasal vaccine provided
near-complete protection against H5N1 infection in both hamsters and mice. As
expected, standard seasonal flu vaccines offered little defense against bird
flu. The nasal spray consistently outperformed the same vaccine formula given
as a traditional injection. Researchers also observed strong protection even
when animals received a low vaccine dose and were exposed to high levels of the
virus.
Delivering the vaccine through the nose produced broad
immune responses throughout the body, with especially strong activity in the
nasal passages and respiratory tract. According to Boon, this method offers a
major advantage over intramuscular shots by providing better protection in the
nose and lungs, which likely reduces both severe illness and the risk of
transmission.
“We’ve shown that this nasal vaccine delivery platform we
conceived, designed and conducted initial testing on at WashU Medicine can
prevent H5N1 infection from taking hold in the nose and lungs,” said Diamond,
the study’s co-senior author. “Delivering vaccine directly to the upper airway
where you most need protection from respiratory infection could disrupt the
cycle of infection and transmission. That’s crucial to slowing the spread of
infection for H5N1 as well as other flu strains and respiratory infections.”
Works Even With Prior Flu Immunity
The researchers also tested whether immunity from previous
flu vaccinations or infections would interfere with the new vaccine’s
performance. Their results showed that the nasal vaccine remained highly
effective even in the presence of existing flu immunity. This is an important
finding, since most people, aside from very young children, already have immune
memory from past influenza exposure.
Next, the team plans to conduct additional animal studies
and experiments using organoids that mimic human immune tissue. They also aim
to refine future versions of the vaccine to further reduce any influence from
past seasonal flu exposure while enhancing antiviral responses.
Reference: “An intranasal adenoviral-vectored vaccine
protects against highly pathogenic avian influenza H5N1 in naïve and
antigen-experienced animals” by Ying B, Pyles K, Darling TL, Seehra K, Pham T,
Huang LC, Harastani HH, Sharma A, Desai P, Kashentseva EA, Curiel DT, Peters B,
Case JB, Strauch EM, Diamond MS, Boon ACM, 30 January 2026, Cell
Reports Medicine.
This study was supported by the Cooperative Center for Human
Immunology (U19AI181103) and the Center for Research on Structural Biology of
Infectious Diseases (75N93022C00035).
The Boon laboratory has received funding from Novavax Inc for the development of an influenza virus vaccine, as well as unrelated funding from AbbVie Inc. M.S.D. serves as a consultant for or sits on the Scientific Advisory Board of Inbios, IntegerBio, Akagera Medicines, GlaxoSmithKline, Merck, and Moderna. The Diamond laboratory has also received unrelated sponsored research funding from Moderna.
