SARS vaccine race

"We do believe we should start with the development of vaccine, and there are quite a few companies going ahead," said Klaus Stöhr, a World Health Organization (WHO) virologist and its chief scientist on severe acute respiratory syndrome (SARS), in a press briefing this week. "But on the other hand, we do believe that it will be much less costly, it will mean much less death and disease for the next 5, 10, 100 years, if we are capable of dealing with this disease now." "This is our one-off chance to get rid of this disease. We don't need another pathogen floating around. We have enough to do with TB, AIDS, malaria, other upper respiratory tract infections, diarrhea, and so on — we don't need another vaccine which is going to be a drain on public health resources," Stöhr explained. Despite WHO's urgent emphasis on "putting the SARS virus back in the box," the disease continues to spread to new areas, and the latest analyses of the new coronavirus provide few clues to its probable animal host. Thus, a vaccine may yet be needed. But it won't be easy, said Stöhr. "If we are in the position that the virus changes very quickly, and that the portion of the virus that creates the immune response is changing, we might be in a position that we would have to update a vaccine as quickly as we do for influenza, which would require similar [constant] global surveillance. We hope that we are not getting that. We are still cautiously optimistic that we can control the disease with the current control measures." Nonetheless, the US biotechnology company GenVec announced last week that it had begun working to apply its adenovirus technology — already in use developing HIV vaccine candidates — to SARS. GenVec's work will take place under an existing contract with the National Institute of Allergy and Infectious Diseases (NIAID). This week, GlaxoSmithKline announced it is in discussions with the Centers for Disease Control and Prevention (CDC) and is also beginning SARS vaccine work. Though GenVec has the first contract to work on a SARS vaccine, NIAID and CDC have been talking with pharmaceutical industry representatives to understand who else will be tackling SARS vaccines. "We aim to get a sense of what kind of research on SARS is going on already and to get an idea about which companies are interested in doing this type of research. Based on this response, due by May 16, we intend to identify the knowledge gaps that exist and define the initiatives that would best respond to these needs," said Sharon Kraft, the National Institutes of Health (NIH) contract specialist administering NIAID's SARS vaccine contract. According to Stöhr, "We are fully supportive to this development. There is no other country [but the United States], so far as we know at the moment, supporting vaccine development, or at least trying to understand the obstacles facing the companies to develop vaccines or antiviral drugs. Currently we know that Chiron is working on a vaccine, and we have indications for some other companies too." WHO is also providing viruses for vaccine and drug development. "All the labs on the WHO collaborative network have helped with the establishment of a vaccine bank for vaccine and drug development, with the provision of viruses from various countries," said Stöhr. "One company [Aventis] gave a validated Vero green monkey cell line to NIH and CDC free of charge. Normally it takes a lot of money and time to develop these lines, so it was a very generous offer. And it is important now that viruses from original clinical material should be made available to put into these cells, for every company to begin with vaccine production if they wish to do so." At GenVec, Chief Executive Officer Paul Fisher told The Scientist that his company's technology involves disabling an adenovirus by removing a series of genes, "typically three," so the virus can't replicate. "Then, we insert the sequences to induce the expression of a new protein that we'd like to produce. The proteins aren't expressed on the surface of the adenovirus — that would be technically more difficult — but we can arrange that when we infect an animal with the construct, the gene goes into the animal cell, and the cell then transiently expresses them as foreign antigen, without expressing other adenovirus genes." The strategy for SARS, Fisher said, "is to take the published sequence, make a synthetic gene from that, and introduce it into the adenovector. Then we can put it in animals, and we typically — but not always — get both a humoral and cellular immune response." GenVec will begin construction "very shortly," said Fisher. "So I would imagine we'd have the first construct within weeks. Then we need to get into animals, which will take some months. The NIH is developing animal models of the disease. And since the Vaccine Research Center is plugged into that, we'll hand the construct back to them for the animal tests." Gary Nabel, director of the NIAID Vaccine Research Center (VRC), told The Scientist that the arrangement was separate from the NIH appeal to industry. "We are funding a contract for GenVec to produce a clinical grade vector, through a cooperative R&D agreement. And we were able to put that into place rather quickly because we work with them on HIV. We had a lot of confidence in their people and a lot of understanding of how we can work together, with real synergies between our various groups.""We are working with the sequence for the SARS spike glycoproteins," said Nabel. "And at my lab in the VRC we've made it synthetically, from synthetic oligonucleotides." "This is part of a wider effort," Nabel added. "There's another group here that's working on an inactivated viral vaccine, and Aventis has been kind enough to donate their Vero cell line that might be used to grow such vaccines. It just so happens that the GenVec agreement has come to closure first." In Europe, scientists are expressing frustration that there has been no support for SARS vaccine development. Peter Rottier of Utrecht University is developing a new vaccine against a fatal feline coronavirus by recombinant modification and disablement of the virus itself. He told The Scientist, "It's annoying that there has been no offer of funding in Europe for the development of a vaccine against SARS. I would have expected the European Union in Brussels to immediately jump on it. If they've set apart any funds for disasters and so on, surely they could use some of them for this. We belong to a network of people who have worked on vaccines for coronaviruses, and we have contacted the EU already. But the response was negative." There is a lot of interest from animal vaccine companies in the feline coronavirus, said Rottier. "We've been concentrating on that for the last 15 years or so. And we've being covering all possible approaches going from classical vaccines to subunit vaccines to DNA vaccines, recombinant vaccines, etc. This is the arena where we'd be able to help with SARS." Vaccine candidates could in principle be tested in monkeys at the Erasmus University in Rotterdam, where research recently confirmed the SARS coronavirus was indeed the cause of SARS.

SARS vaccine race

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