IT COULD soon be possible to temporarily boost people鈥檚 immune systems to
fight off all sorts of diseases, including anthrax. This could help protect
travellers and people undergoing surgery as well as workers or soldiers at risk
from bioweapons.
The method is based on a key difference between human and bacterial DNA. In
people, when the bases cytosine and guanine occur together, the cytosine usually
carries a methyl group. In bacteria, it doesn鈥檛. So when the vertebrate immune
system encounters a 鈥淐pG鈥� sequence containing unmethylated cytosine and guanine,
it immediately mounts a generalised immune response that protects against
bacteria and other pathogens.
Several teams are now developing synthetic CpGs that trigger this response.
They have shown great promise in initial studies. Because a generalised response
is quick and non-specific, it should protect people exposed to a wide range of
bacteria, or to strains against which vaccines don鈥檛 work.
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Unpublished work by Dennis Klinman of the US Food and Drug Administration
shows that immunisation with CpG sequences can protect mice from anthrax. Others
have shown that CpGs completely protect mice from potential bioweapons such as
Ebola, Listeria and tularemia.
The sequences also offer protection against parasitic diseases that could
infect travellers and soldiers, such as those responsible for malaria,
leishmaniasis and schistosomiasis. The studies have shown that CpGs induce an
immune response that limits a pathogen鈥檚 early growth and reproduction.
鈥淚 am convinced that these things are almost ready for prime time,鈥� says
Robert Seder of the National Institutes of Health, who is working on CpGs in
mice. Still, he cautions that: 鈥渨e鈥檒l have to go with this carefully鈥� in people.
Tests on human cells suggests exposure to CpGs does produce good innate immune
responses, but clinical trials have yet to be performed.
However, CpGs have already been tested on people for different reasons.
Companies such as Coley Pharmaceuticals of Massachusetts have been trying to use
CpGs as adjuvants鈥攕ubstances added to vaccines to boost the immune
response. The trials so far show no serious adverse reactions from CpGs, says
spokeswoman Patricia Dimond. Other teams are trying to use CpGs to prevent asthma
(快猫短视频, 2 October 1999, p 17).
Dimond would not say whether Coley Pharmaceuticals is interested in exploring
CpGs as protective agents. But the company鈥檚 chief scientific officer, Arthur
Krieg, has said in the past that CpG DNA 鈥渕ay be a profoundly effective way to
activate the body鈥檚 natural immune defences to provide a broad-spectrum
protection against biowarfare鈥�.