Booster Shot

From Forbes magazine, an article on the encouraging progress being made by pharma companies on the vaccine front:

A new golden age of vaccines is at hand, promising inoculations against malaria, meningitis and much more.

Vaccine researcher Ripley Ballou was an eager human guinea pig. As part of a six-man experiment at the Walter Reed Army Institute of Research in 1987, he had himself injected four times with a genetically engineered malaria vaccine. Then he taped to his arm a styrofoam cup. In it were five mosquitoes infected with malaria.

Ten days later Ballou got violently ill, with uncontrollable chills, profuse sweats and headaches that felt like “a 9-inch spike through my head,” he says. The experimental vaccine protected only one of the six volunteers in the trial. Even after drugs quelled the infection, Ballou felt run-down for weeks.

But that lone success provided inspiration for a far more potent malaria vaccine that 20 years later is finally set to go into giant clinical trials next year at GlaxoSmithkline, where Ballou now works. If successful, it could be the first vaccine for a scourge that has plagued mankind since ancient times. “This vaccine will have a huge impact,” predicts Jean Stephenne, chief of GlaxoSmithkline’s vaccine unit.

Glaxo’s malaria shot is at the forefront of a vaccine renaissance. The revolution in genomics and molecular biology has rescued a segment of the drug industry that for decades was viewed as a low-margin backwater beset by litigation and regulation. Drugmakers are producing vaccines that weren’t possible before–and getting a premium price for them. In diseases for which there is no private vaccine market, such as pandemic influenza, or for which cases are concentrated in poor countries, such as malaria and tuberculosis, governments and public-private partnerships have stepped in to subsidize development.

The resurgence couldn’t have come too soon. Mayo Clinic vaccine researcher Gregory Poland counts more than a dozen new diseases that have emerged in the last few decades: HIV, Lyme disease, West Nile virus, avian influenza. The vaccine boom, he says, “is shaking up the market.”

The $13 billion global vaccine business will grow 18% a year to $30 billion in 2011, predicts Lehman Brothers (nyse: LEH – news – people ), well above the 4.4% annual growth expected for the drug industry overall. Merck (nyse: MRK – news – people ) introduced three new vaccines last year, including Gardasil to ward off cervical cancer, while GlaxoSmithkline promises seven over the next five years, including a Gardasil competitor now awaiting approval from the Food & Drug Administration. AstraZeneca (nyse: AZN – news – people ) bought vaccinemaker MedImmune for $15.6 billion in June, while Pfizer (nyse: PFE – news – people ) last fall bought PowderMed, a British firm testing a needle-free inoculation. Sanofi-Aventis (nyse: SNY – news – people ) spent $150 million for a new plant that will double its flu shot production capacity in the United States to 100 million doses.

A new adult and adolescent vaccine market will make up a big portion of that growth. Diseases such as antibiotic-resistant hospital infections and genital herpes have become hot targets. One company, VaxInnate, is testing a universal flu vaccine that would work against all strains and wouldn’t have to be taken every year. Ultimately, researchers envision shots to stave off chronic diseases such as cancer and atherosclerosis. One exception to the optimism is aids; a promising Merck vaccine failed in a recent study.

Modern vaccines date back to British doctor Edward Jenner’s 1796 work immunizing children using pus from cowpox blisters. Ensuing vaccines were nothing more than a dead or weakened strain of a pathogen such as polio, mumps or measles that trains the body to generate protective antibodies. By the 1980s vaccines had wiped out so many diseases, and vaccine prices had fallen so far, some companies gave up searching for new ones. Vaccines were also dogged by safety issues, including the swine flu vaccine fiasco of 1976, and by the dubious theory of a link between autism and the mercury once used in a vaccine preservative.

But in 2000 Wyeth scored a huge hit with Prevnar, the first vaccine for infants against pneumococcal bacteria, a common cause of pneumonia and ear infections. It uses a clever linking technology to hook together a diphtheria protein to sugars from the surface of seven pneumococcal strains. The resulting compound is easily spotted by the infant’s immune system. Pneumococcal infections in young kids plunged 77% after Prevnar’s debut. Sales should hit $2.5 billion this year, thanks in part to its premium $311 price for four doses. (An influenza shot costs only $15.) Wyeth is testing a second-generation version that covers six more strains.

The subsequent mapping of the genomes of many nasty pathogens has opened up wholly new approaches to vaccine discovery. In the late 1990s Novartis (nyse: NVS – news – people ) researchers decoded the genome of the Neisseria meningitidis B bacterium, which is responsible for one-third of cases of meningococcal meningitis. There are vaccines for other meningococcus strains, but a vaccine for the group B strains had been eluding microbiologists because their surface sugars are identical to human ones. After Novartis sorted through 2,000 proteins in the genomic database, it found five proteins that, when injected into laboratory mice, generated antibodies against at least 66 of 85 group B strains, according to a 2006 study. The vaccine is now in midstage human trials. Wyeth and Sanofi-Aventis have competing efforts.

Austria’s Intercell has spent the last several years gathering blood samples from patients who have survived staph infections to determine which antibodies they had in common. A vaccine based on its findings is now in early human trials at Intercell’s partner Merck.

Malaria is one of the toughest foes of all. The shifty parasite morphs into four different forms once inside the body and spends most of its time hiding inside cells where the immune system can’t get to it. It took Glaxo 20 years to make significant progress with the malaria vaccine that failed to protect Ripley Ballou. First Glaxo researcher Joe D. Cohen took the malaria surface protein used in Ballou’s vaccine and fused it to a protein from the hepatitis B virus, creating a harmless particle that looked like a virus to the immune system. That helped, but not enough. So Glaxo added adjuvants, substances that bolster immune response, including a bacterial wall extract and a detergentlike substance from the soapbark tree. In 1997 it hit the jackpot with an adjuvant combo that protected six of seven volunteers.

In a 2004 trial of 2,000 children in Mozambique the Glaxo vaccine slashed severe malaria cases by about half. Last month a smaller trial in infants (who are most vulnerable to malaria) found it prevented infection in 65%. Now Glaxo is gearing up to test it on 16,000 kids in seven African countries. One huge question is how long the protection will last. Glaxo has already spent $300 million on the vaccine and the Bill & Melinda Gates Foundation has kicked in another $108 million. Trial results could come in 2011. Glaxo is confident of success. It has revamped a giant factory in Belgium to produce tens of millions of doses.

Glaxo’s Stephenne hopes to sell huge quantities of malaria vaccine for a modest profit, while using its adjuvant components for more lucrative vaccines, such as one to prevent lung cancer recurrence. The cancer vaccine is now in final-stage trials.