China in SARS vaccine trial

30 volunteers to receive inactivated virus in Phase I equivalent

John Dudley Miller(johnmiller@nasw.org)
Jan 20, 2004

Chinese researchers are about to begin a human clinical trial of a new severe acute respiratory syndrome (SARS) vaccine developed in that country, according to a high-ranking government official quoted in a Chinese newspaper. The trial would put them at least 5 to 8 months ahead of scientists in other countries attempting to create their own SARS vaccines, but the head of China's food and drug administration said that testing and manufacturing their vaccine will “take time.” Another official at the agency told the newspaper last month that it would take years.

According to a report earlier this week (January 19) in China Daily, Li Xueyong, the Chinese vice minister of science and technology, announced that 30 volunteers will soon be inoculated with the vaccine, created over the past 9 months and recently approved by China's food and drug administration. The vaccine is made of inactivated virus.

The small trial will try to determine whether the vaccine is safe to use in humans, making it roughly equivalent to a Phase I clinical trial in the United States, according to Gary Nabel, director of the US National Institute of Allergies and Infectious Disease's (NIAID's) Vaccine Research Center.

World Health Organization officials said in November that they expect that at least one of the competing SARS vaccines will be available in 1 to 2 years if another epidemic breaks out, but not for 4 or 5 years if one doesn't. That's because final proof that the vaccine works requires vaccinating people who come in contact with SARS patients and showing that their immune systems successfully resist the disease. Right now, China has only three SARS patients—too few to test, Nabel said.

Human clinical trials of vaccines produced outside of China will not start for several months, according to Nabel and another North American SARS researcher. “I think this fall will be the earliest we'll start seeing safety trials,” said B. Brett Finlay, a University of British Columbia professor who leads a team of 40 scientists developing three different types of SARS vaccines. “That's very optimistic,” he told The Scientist.

Nabel said, “If things go smoothly for us, sometime by the summer we might be able to get into a clinical trial” of either of two vaccines his lab is developing. But two other vaccines—ones NIAID is paying Baxter International and Aventis Pasteur to produce—won't start safety trials before “late this year,” Nabel told The Scientist. Neither scientist is aware of any other SARS vaccine projects worldwide that will be begin Phase I trials before this fall.

“What's lacking in the world right now is definitive proof that a vaccine will work in a relevant animal model,” Finlay said. The Chinese researchers inoculated rhesus monkeys, but “most people are finding that [even unvaccinated rhesus monkeys] get a very weak cold, if that” when exposed to SARS.

Nabel said the best candidate animal species now is the ferret, although so far ferrets have only been tested in one laboratory. Despite the weakness of the Chinese animal proof, both scientists said they think the small trial is warranted because of the chance that another SARS epidemic might strike this winter or the next.

However, Chinese officials acknowledged that the vaccine might possibly infect the volunteers with SARS rather than protect them from it, according to China Daily. Finlay said that the inactivation process may spare some RNA that could reverse transcribe back to SARS virus DNA.

In addition, there is a theoretical possibility that antibodies triggered by any SARS vaccine might actually prevent the immune system from recognizing live SARS virus later on, thus helping to infect vaccinated people. This has happened with the vaccine for respiratory syncytial virus, Nabel said, for unknown reasons.