A NEW virus begins spreading around the world. There is no treatment, and many people die. But within weeks, doctors identify effective antibodies against the virus by taking immune cells from people who survive infection. Within months, the antibodies are being mass-produced and injected into anyone at risk, saving lives and helping to halt the outbreak.
This scenario might now be feasible thanks to a very fast method of isolating antibodies, developed by an international team led by Antonio Lanzavecchia at the Institute for Research in Biomedicine in Bellinzona, Switzerland. The researchers have managed to derive potent antibodies against the SARS virus within weeks from a small blood sample. 鈥淭he technique allows us to exploit the immune response of the first person to recover,鈥� says Lanzavecchia.
The approach could be used to derive antibodies for treating diseases such as Ebola, for which there is no effective drug or vaccine, or anthrax, where cases are so rare the risks of vaccinating entire populations outweigh the benefits. Lanzavecchia is also interested in exploring the potential of antibodies against hard-to-treat diseases such as HIV and hepatitis C. In fact, the method will make it much easier to find antibody treatments for anything that any individual produces antibodies against, from toxins such as snake venom to various kinds of cancers.
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Injecting ready-made antibodies into people is a century-old technique known as passive immunisation. It can prevent infections or keep them under control until the patient鈥檚 own immune system kicks in. But antibody products purified from the blood of animals or vaccinated people are not very safe and so are now seldom used.
It is now possible to mass-produce pure human antibodies, but finding potent antibodies against diseases is still a slow, difficult process. Only one factory-made antibody for preventing an infectious disease (respiratory syncytial virus) has reached the market so far.
The ideal place to find antibodies against a particular disease is in people who have survived the illness. Memory B cells carrying the genes for the antibodies that helped defeat the infection stay in the body for the rest of people鈥檚 lives. But getting hold of the right B cells is tricky.
Isolated B cells can be immortalised, or made to grow indefinitely, by infecting them with the Epstein-Barr virus, but this works for only 1 or 2 cells out of 100, so the chances of immortalising ones that produce the desired kind of antibody are slim. This method had been largely abandoned until Lanzavecchia鈥檚 team discovered that adding a kind of DNA called a CpG sequence, which is characteristic of viruses and bacteria (see New 杏吧原创, 10 November 2001, p 6), stimulates the growth of the B cells, ensuring that between 30 and 100 per cent of B cells are immortalised.
As proof of principle, the team took a blood sample from someone who had recovered from SARS. They isolated the memory B cells and immortalised them, and grew groups of 10 cells in small wells. Then they tested the medium in which the cells were grown for antibodies against SARS. 鈥淲ithin 45 days we had a human monoclonal antibody that was better than those developed in a year by other groups,鈥� says Lanzavecchia.
And soon the team had isolated 35 B cell lines, each producing a different SARS antibody. The most potent of these antibodies bind so well to key SARS proteins that they neutralise the virus at concentrations more than 1000 times lower than the antibodies of other groups (Nature Medicine, DOI: 10.1038/nm1080). For commercial production, the genes for the best antibodies could be isolated and engineered into other cells.
The ability to rapidly screen hundreds of different antibodies to find the most potent ones is crucial, says team member Rino Rappuoli of Chiron Vaccines in Siena, Italy. 鈥淭his is the only technology I鈥檓 aware of that can make antibodies for infectious diseases commercially attractive.鈥�
Other methods tend to produce low-affinity antibodies, he says. That means patients would need large doses, and any product would be expensive and hard to deliver. The more potent the antibody, the smaller the dose needed, making products cheaper and deliverable by a simple injection.