HOPES that SARS, like many new viruses, would take badly to its new host and lose virulence are fading. If anything, the virus may evolve into something worse. And many epidemiologists think we are slowly losing the battle to contain it. We might have a year or two before it has spread everywhere. So what defences can we put up in that time?
A vaccine could stop SARS in its tracks. And we already have vaccines that protect animals against viruses similar to the SARS coronavirus. Yet a year is an unimaginably short time in which to develop a vaccine, test its effectiveness and safety 鈥� and get it to people.
Having said that, before SARS it would have seemed far-fetched to suggest that scientists could identify the bug responsible, sequence it and start looking for a remedy within weeks. Major institutions are already gearing up to make the same kind of effort to find a vaccine. They will have plenty of incentive. It now seems likely that the death rate among those infected with SARS could be 10 per cent or more, far higher than the initial estimate of 4 per cent.
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Fortunately, while coronaviruses that infect people have received little attention until now, scientists know a great deal about the kinds that afflict pigs, cows, chickens and cats, where they cause millions of dollars of losses every year. And SARS is closely related to these strains. One end of its genome looks similar to that of viruses which cause severe bronchitis in poultry. The other looks like that of viruses which cause hepatitis in mice, and diarrhoea and pneumonia in cows.
There are vaccines for both cattle and chicken diseases. But what kind would be best for SARS? Many vaccines consist only of proteins from the surface of a virus. When injected into the blood, these teach your immune system to recognise the virus and make antibodies against it. But the main antibodies that are produced, called IgG, may not protect you against a virus that invades not the blood but the epithelial cells that line the lungs.
Despite this, many of the animal vaccines against coronaviruses are made of viral proteins. They work because each is mixed with a substance 鈥� called an adjuvant 鈥� that provokes a much stronger immune response than the viral proteins alone. But adjuvants can trigger nasty side effects such as autoimmune reactions, and despite much effort researchers have yet to find a safe one for eliciting epithelial immunity in people.
Another type of vaccine consists of a live, harmless strain of the virus. Because these infect the epithelium of the nose, lungs or gut, exactly as the original virus would, they elicit exactly the right response: antibodies called IgA, plus a more complex cell-mediated immune reaction.
Peter Rottier of the University of Utrecht is about to publish details of how he protected cats against a coronavirus that causes lethal abdominal inflammation with this kind of vaccine. He made a harmless strain by removing a handful of viral genes that code for non-structural proteins. And the same genes are present in SARS, according to Rob Holt of the British Columbia Cancer Research Centre, the first lab to sequence the SARS virus. Removing them might produce a similarly weakened vaccine. 鈥淚t could work,鈥� he says.
But there is a big concern with live, weakened viruses 鈥� they can swap genes with related viruses. Dutch scientists report that a live coronavirus vaccine, widely used in chickens against infectious bronchitis, has frequently recombined with other coronaviruses. The last thing we need is a vaccine that gives rise to another dangerous disease.
Coronaviruses also mutate at a very high rate, which means that new strains could evolve as soon as a vaccine has been created. In chickens, the bronchitis virus evolved to attack the kidneys, after the vaccine has excluded it from the lungs. It is now a growing problem on chicken farms, says Gary Butcher at the University of Florida, Gainesville.
One way around this would be to put the genes for the proteins most important for immunity 鈥� probably the spike proteins of the corona that gives the viruses their name 鈥� into a less dangerous live virus, such as an adenovirus (a kind of virus that causes the common cold). This would infect the epithelia and elicit the right kind of immunity without recombination with other coronaviruses.
But the biggest problem with any live vaccine for people is the massive safety testing required, says Colin Crouch of Schering-Plough Animal Health in Britain, who helped develop Schering鈥檚 commercial vaccine for bovine coronavirus. Normally, it would take a decade, though if the death toll from SARS becomes high enough regulators may be prepared to cut corners.
It might not come to that. Gus Kousoulas at Louisiana State University at Baton Rouge thinks a simple protein vaccine might just work. His team discovered a bovine coronavirus that causes severe pneumonia in cows. Even more surprising, he says, was that the respiratory infection elicited not just IgA antibodies in the cows鈥� nasal epithelium, but IgG antibodies in their blood, the kind normally elicited by protein vaccines. 鈥淢aybe IgG can provide effective immunity, so maybe a simple protein vaccine will work,鈥� he says.
A protein vaccine would certainly be the quickest to develop. But even this kind of vaccine would take a year or two to test for safety. And once any vaccine was approved, vast new production capacity would be needed to provide enough to meet demand.
As we wait to see if a vaccine can be created, treatment rather than prevention is the best hope for reducing the death toll. Indeed, if infected people could be spotted quickly and treated effectively, we might be able to wipe out the virus without a vaccine.
There are very few antiviral drugs 鈥� the search for chemicals that work against viruses the way antibiotics do against bacteria has generally been disappointing. But some companies are dusting off experimental compounds and re-testing them against SARS. Meanwhile in Hong Kong, doctors say they have saved a few patients by giving them blood serum from SARS patients who recovered, which would contain antibodies to the virus. Antisera used to be collected from infected animals. But safer anti-SARS antibodies might now be produced in cell cultures.
Another possibility is 鈥渁ntisense鈥� therapy. SARS is an RNA virus (see Graphic), so antisense drugs, which consist of short segments of RNA that bind to and block the expression of complementary sequences, might work against it. AVI BioPharma of Oregon may be the first to try this approach. It has created a long-lasting form of RNA that resists being broken down in the body. 鈥淲e鈥檙e checking right now that none of the SARS sequences is similar to any human sequences,鈥� says spokesman David Mason. If they aren鈥檛, he says, 鈥渨e could have an antisense treatment for SARS ready in a couple of weeks.鈥� Last year the company created an antisense sequence in just two weeks to protect penguins at a Milwaukee zoo from West Nile virus, though so far it has not been needed.
Making enough of such a drug in a short time will require the resources of one of the pharmaceutical giants. The chances are it will also be expensive. The poor countries where SARS is most likely to run out of control are unlikely to be able to afford any treatments that become available, as with AIDS. Then again, no other disease in recent years has posed such an immediate threat to the global economy. That might just persuade the rest of the world that it cannot afford not to make any effective treatment available to all.