Palese, Sastre :Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

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doi: 10.1128/​ mBio.00018-10 18 May 2010 mBio vol. 1 no. 1 e00018-10


ABSTRACT

Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.

IMPORTANCE Current influenza vaccines are effective against only a narrow range of influenza virus strains. It is for this reason that new vaccines must be generated and administered each year. We now report progress toward the goal of an influenza virus vaccine which would protect against multiple strains. Our approach is based on presentation to the host immune system of a region of the influenza virus?called a ?headless hemagglutinin? (headless HA)?which is similar among a multitude of diverse strains. We show that vaccination of mice with a headless HA confers protection to these animals against a lethal influenza virus challenge, thereby demonstrating the viability of the approach. Through further development and testing, we predict that a single immunization with a headless HA vaccine will offer effective protection through several influenza epidemics.

full article:

http://mbio.asm.org/content/1/1/e00018-10.full.html.

 

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Re: Palese. Sastre :Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

Re: Palese. Sastre :Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain

Researchers take step to 'universal' flu vaccine


Vaccine protects against multiple flu strains



By Maggie Fox, Health and Science Editor

WASHINGTON, May 25 (Reuters) - A "headless" version of the influenza virus protected mice from several different strains of flu and may offer a step towards a so-called universal flu vaccine, researchers reported on Tuesday.

They identified a piece of the virus that appears to be the same even among mutated strains, and found a way to make it into a vaccine.

Years of work lie ahead but if it works in people the way it worked in mice, the new vaccine might transform the way people are now immunized against influenza, the team at the Mount Sinai School of Medicine in New York reported.

"We now report progress toward the goal of an influenza virus vaccine which would protect against multiple strains," Dr. Peter Palese, Dr. Adolfo Garcia-Sastre and colleagues report in a new journal mBio, available here

"Current influenza vaccines are effective against only a narrow range of influenza virus strains. It is for this reason that new vaccines must be generated and administered each year."

Flu viruses mutate constantly and each year a cocktail of three flu vaccines is tweaked to try and hit the most common new mutations. Every few decades a new pandemic strain emerges -- a year ago the new H1N1 swine flu strain started a pandemic and it has been added to the seasonal flu vaccine mix.

It takes months to make a new flu vaccine and governments and commercial drug companies struggled to get the new H1N1 vaccine out by last September. Having a universal flu vaccine could, in theory, prevent future pandemics and keep seasonal flu under better control.

VULNERABLE NECK

Palese's team focused on an important piece of the flu virus called hemagglutinin. This mushroom-shaped structure helps the virus attach to the cells it infects and gives flu viruses the "H" in their names.

The "neck" of hemagglutinin does not mutate the way more visible bits of the virus do, and if there was an easy way to help the immune system to see it, this provides a good antigen -- a target for a vaccine.

But the top, umbrella-shaped part of the hemagglutinin protein hides this vulnerable neck from the immune system. Palese's team found a way to get to the neck, cut it out and make a vaccine out of it

"A headless hemagglutinin molecule could form the basis for a broadly protective influenza virus vaccine," the researchers wrote.

"This paper is more proof of concept," Garcia-Sastre said in a telephone interview. "We don't think we have yet the most optimal way to display the antigen."

Tests in mice showed the vaccine protected them from otherwise lethal doses of multiple strains of influenza.

Garcia-Sastre's team made a plasmid, a circular piece of DNA, for their vaccine but other ways to do it include a virus-like particle, used in other vaccines, or bits of DNA made by a baculovirus, he said. He said they are open to working with a drug company on this.

Flu infects up to 10 to 15 percent of the U.S. population each year, more in a pandemic year, and kills an estimated 36,000.

Dozens of companies make influenza vaccines and bring in millions of dollars in revenues from them. The United States, for instance, bought 162 million doses of H1N1 vaccine from five makers -- Novartis (NOVN.VX), AstraZeneca (AZN.N) unit MedImmune, Sanofi Aventis (SASY.PA), GlaxoSmithKline (GSK.L) and Australian vaccine maker CSL (CSL.AX). (Editing by Eric Walsh)

http://uk.reuters.com/article/idUKN2520541320100525