Experimental bird flu vaccines show promise in early trials

Reuters

* Novartis, Novavax H7N9 vaccines give good immune response

* Companies using new technologies to accelerate production

* H7N9 flu emerged as human threat in China last winter (Updates with details on Novartis vaccine)

By Sharon Begley and Ben Hirschler

NEW YORK/LONDON, Nov 14 (Reuters) - The first human tests ofexperimental vaccines against a deadly strain of avian flu,using novel technology that could produce millions of doses veryquickly, has produced protective antibodies in the vast majorityof recipients.

Encouraging results in early-stage trials were announced forseparate vaccines from Swiss drugmaker Novartis andNovavax, a biotech company based in Rockville,Maryland.

Details of the Novavax vaccine were published online in theNew England Journal of Medicine late on Wednesday, whileNovartis disclosed its positive findings on Thursday.

"These are very preliminary results, but it appears for thefirst time that we may have a vaccine that would work against anoutbreak" of avian flu, said Robin Robinson, director of the Biomedical Advanced Research and Development Authority, orBARDA, the federal agency in charge of developingcountermeasures against public health emergencies.

Because other candidate vaccines against avian flu havefailed, "this is a very important milestone", he said. "We havea promising vaccine where before we had none."

The H7N9 strain of avian flu emerged in China last winter.There had been 45 deaths from 137 confirmed cases this year asof late October, according to the World Health Organisation.Cases and deaths, often from severe pneumonia, both peaked inMarch and April.

But public health experts fear the virus could come stormingback this flu season. After no reported cases of H7N9 in Chinain August or September, there have been four since earlyOctober.

A mortality rate of one-third suggests the virus is highlylethal.

The WHO says there is currently "no indication" the viruscan be transmitted from person to person, and so cannot become apandemic. But flu strains can quickly undergo genetic changesthat make them transmissible between people.

In the Novartis clinical trial, 400 healthy adult volunteersreceived two doses of either a dummy injection (placebo) ordifferent formulations of the experimental vaccine - either withor without an adjuvant, a chemical compound that turbo-chargesthe immune system.

Of those given the adjuvanted vaccine, 85 percent had aprotective immune response, against only 6 percent for thosegetting the vaccine without the adjuvant.

The Novavax study involved 284 volunteers who also receivedvaccine formulations with or without an adjuvant.

At the heart of the vaccines are two proteins, dubbed H7 andN9, that stick out from the virus and give it its name. TheNovavax vaccine triggered production of antibodies against the"H" protein in 81 percent of the volunteers who received thevaccine with the high level of adjuvant, and antibodies againstthe "N" in more than 90 percent.

Antibodies are molecules produced by the immune system thatattack invaders.

The studies did not expose volunteers to the virus, which isconsidered unethical, to see if the antibody levels warded offinfection. "But these antibody levels are very likely to beprotective," said Dr Louis Fries, Novavax's vice president forclinical and medical affairs, who led the Novavax study.

Andrin Oswald, head of Novartis Vaccines, said he believedthe Novartis vaccine was "able to offer a protective solutionfor a potentially deadly pandemic virus".

FAST MANUFACTURING

Just as important as the new vaccines' apparent efficacy ishow quickly they can be produced, thanks to eliminating the needto use chicken eggs as most flu vaccine production does.

Fast manufacturing is important because a pandemic flustrain can emerge with little warning. An initial outbreak of anew flu strain is often followed by a more severe and widespreadoutbreak the following flu season.

Novartis has been an early pioneer of full-scalecell-culture manufacturing, an alternative to egg-based fluvaccine technology that can accelerate production significantly.

Novavax uses a process that takes the virus's geneticsequence and produces what it calls a "virus-like particlevaccine".

Virus-like particles, or VLPs, contain three proteins thattrigger the production of antibodies and other immune responsesto thwart the virus. The H and N proteins generate antibodiesthat keep the virus from replicating and infecting cells, whilea third protein stimulates killer T cells to slay any cellsalready infected.

Using Novavax's technique, said BARDA's Robinson, computermodels suggest manufacturers could produce the first doses ofH7N9 vaccine within 12 weeks of the emergence of a pandemic, 50million doses within four months, and hundreds of millions ofdoses within six months.

Novavax has a three-year, $97 million contract with BARDA todevelop recombinant influenza vaccines and manufacturingcapabilities sufficient to produce enough vaccine for apandemic. It is planning a second trial of the VLP vaccine inearly 2014 to nail down the minimum effective dose, said Fries.

Novartis has also received funding from BARDA for itsresearch.

Other candidate H7N9 vaccines are being developed, saidRobinson, with results expected in four to six months. If theyalso work, public health authorities around the world would havemultiple vaccines to choose from should an avian flu pandemicemerge. (Editing by Peter Cooney and Pravin Char)

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