Jab against one strain might worsen infection with others.
A cautionary note has been sounded for those developing vaccines against severe acute respiratory syndrome (SARS). Some vaccines could prove useless against certain strains, or even worsen the infection, a preliminary study suggests.
SARS killed nearly 800 people when it emerged from China in 2002 and spread around the world in the first half of 2003. Only a handful of isolated outbreaks have been spotted since that initial epidemic.
Aware that the disease could re-emerge, several groups have been trying to make a vaccine against the virus. They are mainly trying to find ways to expose people to a protein on the virus's coat, called the spike protein, which helps it to enter cells. This should jolt the immune system into recognizing the virus during a future infection and making antibodies that attack it.
In the new study, Gary Nabel of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and his co-workers injected mice with spike protein from a SARS virus taken from a human patient infected in early 2003. They then collected the antibodies the animals produced.
In lab experiments, they showed that these antibodies were unable to attack spike protein from a different strain of SARS, isolated from a patient infected in late 2003.
The team next tested whether the antibodies would attack spike proteins from two SARS strains isolated from civets, from which the virus is thought to have originally jumped into humans. In this case, they found hints that the antibodies actually boosted the ability of the virus to infect cells. The study is published in the Proceedings of the National Academy of Science1.
The results show that the virus changes over time, so that a strain that crops up in one outbreak might be quite different from that in a later outbreak. "This virus is not standing still and we need to take this into account," Nabel says.
“This virus is not standing still. We need to take this into account. Gary Nabel , National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.”
This raises the prospect that a vaccine against one strain of SARS virus could prove ineffective against others. Worse, a jab against one strain might even aggravate an infection with SARS virus from civets or another species. "It's obviously a concern," Nabel says.
The experiments are still preliminary: there is no sign from those testing vaccines in animals that they actually worsen an infection. But Nabel cautions that researchers should watch carefully for signs this is happening.
He adds that some pilot vaccines, such as one he is testing in a small human clinical trial, could get around the problem because they also provoke other parts of the immune system to cripple the virus.
Find the mechanism
This would not be the first case where exposure to one strain of a virus can worsen infection with another. In the mosquito-borne disease dengue fever, for example, people who have been infected with one strain are likely to suffer a worse infection if they pick up a second strain.
In the case of SARS, it remains unclear how antibodies might be helping some viral strains into cells. "It's an interesting phenomenon," says Chris Olsen who studies animal viruses related to SARS at the University of Wisconsin-Madison. Figuring this out might thwart potential problems in vaccines, he says.
Yang, Z-Y. et al. Proc. Natl Acad. Sci. USA published online doi:10.1073/pnas.0409065102 2005. http://www.pnas.org/cgi/doi/10.1073/pnas.0409065102
National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.