Scientists solve failed vaccine mystery

Dec 15, 2008

Research led by Johns Hopkins Children's Center scientists has figured out why a respiratory syncytial virus vaccine used in 1966 to inoculate children against the infection instead caused severe respiratory disease and effectively stopped efforts to make a better one. The findings, published online on Dec. 14 in Nature Medicine, could restart work on effective killed-virus vaccines not only for RSV but other respiratory viruses, researchers say. The new findings also debunk a popular theory that the 1966 vaccine was ineffective because the formalin used to inactivate the virus disrupted critical antigens, the substances that stimulate the production of protective antibodies.

Instead, researchers said, the problem occurred when the antibodies created by the vaccine failed to successfully bind to the real virus after exposure to it, thereby incapacitating it. Like vaccines against influenza and polio, the 1966 formalin-inactivated RSV vaccine produced antibodies, but these turned out to be defective ones with poor virus-binding ability.

"We have found the root cause of the problem, and in doing so we have uncovered clues that will help us design even safer and more effective vaccines in the future," says senior investigator Fernando Polack, M.D., an infectious disease specialist at Hopkins Children's.

More specifically, in a series of experiments, the research team discovered that the old RSV vaccine failed to trigger a "signaling" mechanism — called toll-like receptor activation — that helps the immune system recognize a virus and mount a defense against it. Toll-like receptor activation is the first in cascade of immune system responses that occur after infection, firing off signals to other immune cells telling them to produce and release antibodies.

First, the team compared immune system response in three groups of mice: those vaccinated with a placebo, those with a weakened form of the RSV virus, and those with inactivated or killed-virus vaccines. Researchers found that in the last group, the toll-like receptor activation was weak and led to the production of defective antibodies.

Next, they infused the vaccine with a substance that stimulates toll-like receptor activation to see if it would created antibodies better equipped to bind to and neutralize the virus. Indeed, mice vaccinated with the toll-like receptor stimulating form of the inactivated vaccine produced antibodies with better binding and virus-neutralizing ability. Mice immunized with this form of the vaccine had milder symptoms and less inflammation in the bronchi and the lungs when infected with the real RSV.

Source: Johns Hopkins Medical Institutions

Explore further: US scientists make embryonic stem cells from adult skin

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.