Fast computerized vaccine might protect against any pandemic flu

Revolutionary method promises human pandemic vaccine “within a month or two” of virus sequencing.

H5N1 bird flu now in Nigeria will kill chickens, and even some people, but it is not pandemic human flu. Nevertheless a pandemic may emerge anytime, anywhere – from a related virus created by its recombination with ordinary human influenza. Response needs to be fast, and now a new genetic method is claimed to be able to create a vaccine within two months of sequencing.

by Prakash Khanal (March 06)

Eggs. They’ve been the problem with existing influenza vaccines. They must be grown in chicken eggs, a process that takes half a year to a year to create enough vaccine for the world’s usual winter round of ‘flu.

But now a new methodology using computerized genetic manipulation promises a vaccine which “can be made quickly – within a month or two” Simon Barratt-Boyes, Associate Professor, Department of Infectious Disease and Microbiology, University of Pittsburgh Graduate School of Public Health, told RealHealthNews.

“It just requires the sequence of the influenza virus to be cloned into an adenovirus [one of the causes of the common cold]. And we can do this from scratch by synthesizing the gene from a published sequence of the virus taken from the computer,” he said.

A variety of influenza viruses is now being sequenced at the rate of two or three viruses a day by the Institute for Genomic Research TIGR, by the Influenza Genome Sequencing Project at the US National Institute of Allergies and Infectious Diseases, NIAID, and by other institutions, so a pandemic virus should be quite swiftly sequenced.

“The genetic sequence of the influenza haemagglutinin gene [coding for the haemagglutinin surface protein] is then cloned into a replication-defective adenovirus which expresses the gene in immunized indivi-duals,” said Barratt-Boyes. Using the existing bird flu virus, “the vaccine also stimulates several lines of immunity against H5N1. The adenoviral vector is very immunogenic, and a single dose will induce a good immune response”.

At least these are the results of trials in mice and chickens at the US Centers for Disease Control, which is collaborating in the research with medical researchers from University of Pittsburgh Medical Center. The work was published in the Journal of Virology in February.

Birds were protected from a lethal challenge with influenza virus, but small amounts of virus were still recovered from some tissues and the oral cavity. Whether this small amount of virus is sufficient to transmit infection to other birds is not currently known. A further concern is that many people have pre-existing immune responses to the adenovirus itself, which limits its effectiveness, so new stereotypes of adenovirus are being investigated to overcome this problem.

Before proceeding with clinical trials the researchers would like to know a little bit more about what causes protection in the animal, and whether it is antibody-mediated or cell-mediated.

Simultaneously they are seeking funding for safety testing in a Phase I clinical trial. According to Barratt-Boyce, if funding is received, they will begin locally with volunteers. Barrat-Boyce believes “there will be absolutely no risk as the adenovirus is completely safe, and the single influenza virus gene in the vaccine cannot cause disease. They will not be challenged with influenza”.

If all goes well Phase I could begin and could be completed within six months. Phase II-III, determining the effective dose, and the actual protection against disease, would then take place in Vietnam, China, Thailand or Cambodia where bird flu is a significant menace to humans. Perhaps Turkey, Greece, Italy and now Nigeria, where H5N1 has recently been identified, could be added to the list.

If successful, this would then have created not just a human H5N1 vaccine effective against the current bird ‘flu – which, remember, has only killed a few dozens of people and is not a pandemic strain – but a new methodology and principle for creating a true pandemic vaccine very quickly. But this would raise a fundamental point of principle, practice – and risk. Given the pandemic virus sequence, and the adenovirus construct, a vaccine could be made and in production within weeks, as it will be produced in cells in the lab, rather than chicken eggs.

But it would be a new vaccine, normally requiring a full series of clinical trials, lasting months or years. But for a world in the midst of a pandemic, that would be too late. So there would be a difficult decision by the US Food and Drug Administration and other such bodies approving pharmaceuticals and vaccines on what tests – if any – should be applied before the vaccine would be approved for use.

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