Pitt researchers pursue SARS vaccination

Last year, Pitt researchers completed the first published trial of a severe acute… Last year, Pitt researchers completed the first published trial of a severe acute respiratory syndrome, or SARS, vaccine on monkeys, and they will soon be ready to test it on human volunteers, according to the leader of the research team.

“We’ve started writing clinical protocols and are moving in that direction as quickly as possible,” said head researcher Dr. Andrea Gambotto, referring to a clinical trial on humans.

The vaccine being tested was not engineered using any part of the SARS virus. It attempts to build immunity to the virus that spreads SARS by infecting the body with mild pathogens that are similar. It is impossible that volunteers will contract SARS from the clinical test.

According to Gambotto, volunteers will have only little risk of being harmed in any other way from the testing and the trial should be very safe, though the research targets a deadly disease.

SARS is a mysterious disease that causes fever, body aches and extreme breathing problems.

The syndrome was never seen in humans before last February, when an outbreak occurred in China. By May, SARS was an international health crisis, having spread through international air travel. The disease affected China, Singapore, Taiwan and Canada most seriously, though more than 30 countries reported SARS cases, according to the World Health Organization.

Quarantines and travel advisories halted the epidemic, but not before 774 people died and more than 8,000 were infected. A few cases have been reported in recent months, but none have been confirmed.

Standard antiviral drugs have not been effective against SARS, and experts are unsure of how to treat it. Researchers do know, however, that SARS is spread by a coronavirus, a member of the virus family that includes the common cold.

This finding led to the vaccine being tested at Pitt.

“We tricked the immune system to generate a SARS coronavirus immunity using a cold virus,” Gambotto explained.

Gambotto and his team engineered an adenovirus, with parts of a cold virus spliced into it. Adenoviruses are small viruses capable of infecting most organic cells with little discomfort to the test subject, making the virus type a valuable tool for such research.

The theory behind the vaccine was that the subject’s immune system would fight the adenovirus, and then develop a general immunity to coronaviruses – including the one that causes SARS.

In June, Gambotto’s team used funding from the National Institutes of Health to test the vaccine on six rhesus macaques, a type of monkey. In August, his team discovered that the animals had developed a general immunity to coronaviruses.

In December, Gambotto and his team published their findings in The Lancet Medical Journal. This was the first published testing of a SARS vaccine, but its importance was somewhat reduced by the discovery, made a few months earlier, that monkeys are an unsuitable test subject for a SARS vaccine.

“Our experience working on an HIV vaccine showed that the closer you go to humans in your animal model, the more chance you have of finding a good model, but this was not the case for SARS,” Gambotto said.

In July, when Gambotto had already begun to test monkeys, researchers at the University of Rotterdam in the Netherlands discovered that, even if infected with the SARS coronavirus, monkeys do not develop SARS.

“The final proof that the vaccine is working is to challenge the animal with the actual virus,” he said. “But this was not possible because monkeys do not get sick with SARS.”

In October, the researchers at Rotterdam discovered that ferrets are much more similar to humans in their response to the SARS coronavirus.

“We are in the process of starting the same experiment [we did on the monkeys] on ferrets, which is very important before we move the vaccine to humans,” Gambotto said.

Gambotto has established a correspondence with the researchers at Rotterdam, who are also testing a vaccine on ferrets. He said that the ferret study will be another opportunity to detect any toxicity in the vaccine. Also, if the vaccine fails to prevent the ferrets from contracting SARS, the team will already know it will not likely be effective for humans.

Meanwhile, Gambotto has already planned a trial using human volunteers and is waiting for the completion of the ferret study, approval from the Food and Drug Administration and additional funding. His team must also engineer an ideal vaccine to be used in the study – the process could take as many as six months.

“These are all things you do in parallel, so you don’t wait for one or the other first,” Gambotto said.

Gambotto predicted that his team would be ready to begin testing human subjects sometime between June and December of this year.

Gambotto said that the most significant risk to volunteers is the minor chance that the vaccine itself would be discovered to be toxic.

“This is not done with the actual SARS virus, so there is no risk to become infected with SARS,” he said. “It would be a different story if we proposed a vaccine like the Chinese vaccine, which is an inactivated virus. Then there is a chance, even though limited, that you could get infected, and it would be more difficult to convince people to become volunteers.”

Gambotto acknowledged that the media attention concerning SARS might initially turn away potential volunteers, but he expects that volunteers will be comforted when they learn of the impossibility of contacting SARS and improbability that the vaccine will making a person ill in some other way,

“Usually it is not difficult to find people who are willing to test,” Gambotto said. “But, of course, you have to inform them.”

-Staff writer Michelle Scott assisted with this story.