Claim: Large quantities of avian flu vaccines in 12 weeks instead of 20-28 weeks

jorgemata — Tue, 17 Jun 2008 04:44:27 -0700

Description

Baxter has successfully produced H5N1 influenza vaccine in African green monkey kidney cells in quantities sufficient for clinical testing, according to an article published in The New England Journal of Medicine.

Patients in the Phase I and II studies responded favourably to the treatment, which could pave the way for increased usage of cell culture-derived vaccines for treating seasonal and avian influenza.

The use of cell culture to produce the vaccine offers considerable advantages over traditional hens' eggs, which could better equip the world to tackle a flu pandemic should it arise.

John Oxford, professor of Virology at Queen Mary School of Medicine, London said: "Cell culture technology could represent the future of influenza vaccine production. Baxter has demonstrated the ability to rapidly make large quantities of the vaccine that may protect people against divergent H5N1 viruses."

[...]

Whether cell culture represents a significant breakthrough in preparations against an avian influenza outbreak remains to be seen. At present there are those that believe that an overarching strategy is needed more urgently than different approaches to the problem.

Link to the full article is below.

J M

Source

Nick Taylor: Baxter uses cell culture for H5N1 vaccine. In-Pharma Technologist, June 17, 2008.
http://in-pharmatechnologist.com/news/ng.asp?n=85946-baxter-h-n-cell-culture-avian-influenza

H5N1: we should stockpile several antiviral drugs to keep open options for effective drug-combination treatments

jorgemata — Wed, 14 May 2008 13:04:52 -0700

Description

Stockpiles of antiviral drugs are an important weapon against the threat of an influenza pandemic, particularly if the deadly H5N1 avian influenza virus moves in earnest into the human population. The problem is which drugs should be amassed, given the notorious mutation rate of influenza viruses and their rapid transformation into drug-resistant variants. A paper in this week's Nature tackles this conundrum by solving the molecular basis of resistance in samples taken from H5N1-infected patients.

Oseltamivir (Tamiflu) and zanamivir (Relenza) are the drugs in the armoury so far - with oseltamivir being stockpiled against any future outbreak. Both target the viral protein neuraminidase, which helps release newly made viruses so that they can spread to uninfected host cells and propagate the infection. Steven Gamblin and his colleagues have studied the detailed structure and properties of neuraminidase mutants from H5N1 patients. They found that the mutants were resistant to oseltamivir but still strongly inhibited by zanamivir.

On the basis of their results, the team advise against stockpiling only supplies of oseltamivir, suggesting that these should be augmented with other antiviral drugs, including zanamivir, keeping open options for effective drug-combination treatments.

The abstract says (citations omitted):

The potential impact of pandemic influenza makes effective measures to limit the spread and morbidity of virus infection a public health priority. Antiviral drugs are seen as essential requirements for control of initial influenza outbreaks caused by a new virus, and in pre-pandemic plans there is a heavy reliance on drug stockpiles. The principal target for these drugs is a virus surface glycoprotein, neuraminidase, which facilitates the release of nascent virus and thus the spread of infection. Oseltamivir (Tamiflu) and zanamivir (Relenza) are two currently used neuraminidase inhibitors that were developed using knowledge of the enzyme structure. It has been proposed that the closer such inhibitors resemble the natural substrate, the less likely they are to select drug-resistant mutant viruses that retain viability. However, there have been reports of drug-resistant mutant selection in vitro and from infected humans. We report here the enzymatic properties and crystal structures of neuraminidase mutants from H5N1-infected patients that explain the molecular basis of resistance. Our results show that these mutants are resistant to oseltamivir but still strongly inhibited by zanamivir owing to an altered hydrophobic pocket in the active site of the enzyme required for oseltamivir binding. Together with recent reports of the viability and pathogenesis of H5N1 and H1N1 viruses with neuraminidases carrying these mutations, our results indicate that it would be prudent for pandemic stockpiles of oseltamivir to be augmented by additional antiviral drugs, including zanamivir.

Source

Crystal structures of oseltamivir-resistant influenza virus neuraminidase mutants. Patrick J. Collins1, Lesley F. Haire1, Yi Pu Lin1, Junfeng Liu1, Rupert J. Russell2, Philip A. Walker1, John J. Skehel1, Stephen R. Martin1, Alan J. Hay1 & Steven J. Gamblin1. Nature, May 14, 2008, http://dx.doi.org/10.1038/nature06956

1 MRC-National Institute for Medical Research, Mill Hill, London
2 Interdisciplinary Centre for Human and Avian Influenza Research, School of Biology, University of St Andrews, Fife, UK