(Repeats INSIGHT first released earlier on Feb. 1)
By Julie Steenhuysen
CHICAGO, Feb 1 (Reuters) - After nearly 100 years,researchers could be on the verge of finding a vaccine thatwould eradicate tuberculosis infections, a scourge that kills1.4 million people a year.
Global health experts are eagerly awaiting clinical trialresults, expected early next week, of the first new vaccine in90 years designed to prevent tuberculosis infections. While itmight not prove effective, it will bring scientists much closerto creating a new generation of TB vaccines.
Known as MVA85A, the vaccine is the farthest along of morethan a dozen candidates being developed globally to stop thetransmission of mycobacterium tuberculosis, which is quicklyoutsmarting the best antibiotic weapons used against it.
"In my own personal view, I will consider this (trial) to bea landmark or a watershed," said Peggy Johnston, senior programofficer at the Bill & Melinda Gates Foundation in Seattle.
"If it is negative, it would be the first trial we candemonstrate that yes, we can conduct a clinical trial and get asolid answer. If it turns out to be at all positive, it will bea clear watershed for the field."
Although companies are making strides developing new drugsto fight TB, such as Johnson & Johnson's recentlyapproved drug, bedaquiline, experts believe a vaccine ultimatelywill be the best tool to eradicate the ancient disease, whichinfects 9 million people a year.
"Drug development at the moment is lagging the rate at whichdrug resistance is emerging. We can't constantly be chasingafter the next drug that becomes ineffective," said ChristineSizemore of the National Institute of Allergy and InfectiousDiseases, a part of the National Institutes of Health.
Dr. Ann Ginsberg of Rockville, Maryland-based Aeras, anon-profit biotech developing MVA85A said it is "the single toolthat could have the greatest potential impact on the TBepidemic."
Ginsberg said better drugs will be useful to treat peoplewho are already sick, but by the time a person with TB isdiagnosed, they have already infected 10 to 15 people.
"A vaccine can stop transmission," she added.
NEW GENERATION OF TB VACCINES
A lot is riding on the trial's results, which will give thefirst solid clues about whether scientists are on the righttrack to create a new generation of TB vaccines.
MVA85A is being developed by researchers at Britain's OxfordUniversity with support from Aeras, the Wellcome Trust, theEuropean Commission and the Oxford-Emergent TuberculosisConsortium, a joint venture between Oxford and EmergentBiosolutions Inc created to make the vaccine.
It is one of 16 vaccines being studied in human clinicaltrials and the study results will inform the design of more than50 vaccines being tested in preclinical trials in animals.
Most of the development has occurred in the last decade withthe emergence of drug-resistant TB, which could affect as manyas 2 million people by 2015, according to the World HealthOrganization.
Treating typical TB is a long process, with patients needingto take a cocktail of antibiotics for six months. Many fail tocomplete treatment and that has given rise to drug resistance.
Multi-drug resistant TB withstands two standard drugs, but amore severe form known as extensively drug-resistant TB, whichthwarts the most highly effective drugs, was reported in atleast 77 countries in 2011, the WHO said.
And doctors in India have begun reporting cases of totallyresistant TB, in which no effective drugs are available.
"This previously neglected disease has now come to theforefront," said Johnston of the Bill & Melinda GatesFoundation, which provides the bulk of the funding for Aeras.
"That has stimulated new investment not only in new drugs totreat those resistant strains, but also in vaccines to give us alonger-term solution."
Part of what makes TB so difficult to treat is that it hasevolved along with humans and hides in human cells.
"Mycobacterium tuberculosis is a wily foe," Ginsberg said."A third of the world is already infected with this bug and some10 percent will get sick and pass it on to others."
It is that large reservoir of future TB cases that vaccinemakers hope to protect, along with those who have never beenexposed.
BUILDING BETTER VACCINES
First used in 1921, the current vaccine, known as BacilleCalmette-Guérin, or BCG, is given routinely to babies incountries with high rates of TB to prevent severe disease.
But protection wears off in just a few years and BCG doesnothing to protect against the most common form of tuberculosisthat invades the lungs of adults and adolescents, and can betransmitted through coughing and sneezing.
For the midstage study of MVA85A, researchers tested nearly3,000 babies in South Africa already vaccinated with BCG. Halfof the babies got the vaccine and half got a placebo.
The goal is to see if babies who got both vaccines werebetter protected than babies who just got the BCG jab.
South Africa offers a unique location for the study. About 1percent of the population develops TB every year, compared with.01 percent in the United States, said Professor Willem Hanekomof the University of Cape Town and co-director of the SouthAfrican Tuberculosis Vaccine Initiative.
"We are in a soup of TB basically in South Africa," saidHanekom, who led the vaccine's trial in the country.
The vaccine is a modified version of a smallpox virus thathas had "its guts ripped out," making it harmless, but stillcapable of evoking an immune response.
Researchers then added a component of TB bacteria to trainthe immune system to fight infection. If the trial succeeds, a larger phase 3 study will be needed before it can be licensed.
Although the vaccine is the most advanced, two others - onebacked by Aeras and GlaxoSmithKline Plc and the other byAeras and J&J's Crucell vaccine unit - are close behind.
Of the two, the Crucell vaccine most resembles MVA85A, using a strategy in which the immune system is primed by the BCGvaccine and then boosted by the new vaccine.
Like MVA85A, Crucell uses a virus - in this case a coldvirus - to transport bits of the TB bacteria or antigen into thebody. But Crucell uses three TB antigens and a different virus.
The GSK vaccine, called M72, is different in that it relieson an adjuvant - a type of booster that revs up the immunesystem - coupled with proteins from the TB virus.
LOTS TO LEARN
Scientists are wary about predicting success for any of thelate-stage candidates.
"At the moment, if you had to ask me which are the mostpromising and which are the least promising, we just don'tknow," Hanekom said.
That is because the basic science underlying TB is so poor, he said, noting that scientists are still unsure exactly whatsignals in animals will predict success in people.
TB vaccine makers also lack so-called immune correlates ofprotection, which are markers that a vaccine has worked, such asthe production of antibodies after a person has been vaccinated.
Correlates of protection allow scientists to screenpotential vaccine candidates in the lab. Without them,researchers are forced into big, costly clinical trials.
"The bottom line is one needs an effective vaccine," Hanekomsaid.
Short of that, Hanekom and others are trying to findcorrelates of protection by following groups of individuals andchecking for changes in their blood as they develop TB.
All of this development has happened within the last 10years, largely due to the efforts of various activist groupssuch as the Gates foundation through Aeras, the NationalInstitutes of Health, the Wellcome Trust and others.
Steve Lockhart, senior vice president of vaccine developmentat Emergent, which has a joint venture with Oxford tomanufacture the MVA85A vaccine, lauded the efforts of the Gatesfoundation and others for bringing the field along.
"No one could justify going to shareholders and having acompany solely take the responsibility for developing this,knowing there is not much of a market at the end," he said.
He said the vaccine might have a modest market in middleincome countries, such as India, China, South Africa and Brazil.
There are efforts to shed light on the market, but KariStoever of Aeras said it could be worth billions by 2027 or2030, when there is an 84 percent chance of having a vaccine.
Sizemore of the NIH said that, even if the trial fails, itwill represent a success.
"From a scientific perspective, we almost can't lose," sheadded. (Reporting by Julie Steenhuysen; Editing by Jilian Mincer andAndre Grenon)
Glaxosmithkline (GSK)