EARLIER THIS month, two biotechnology companies, one based in the United States and the other in Hyderabad, announced a strategic alliance to "pursue the rapid development of pandemic influenza vaccine for India" and certain other markets. Their pandemic vaccine would be based around an efficient manufacturing process for "virus-like particles” according to Novavax and Bharat Biotech.
 Most of the influenza vaccine produced today, much of it in the U.S. and Europe, is based on technology dating back to the 1960s and even the 1940s. A cumbersome process is used to produce a suitable “seed strain” of the flu virus, which is then grown in fertilized chicken eggs. Extracts from the eggs are purified to produce the vaccine. As a paper that appeared recently in the journal Emerging Infectious Diseases pointed out, if 100 million doses of the vaccine have to be prepared, the manufacturer must procure 100 million eggs, and the vaccine takes several months to produce.
It would be impractical to rely wholly on this well-tested but time-consuming method for producing vaccines against pandemic influenza that might emerge suddenly and, then spread rapidly right across the world, infecting and killing people in large numbers. Moreover, no one can predict which strain of the flu virus might set off a pandemic or when such a pandemic might happen. The H5N1 strain of bird flu arouses the greatest anxiety because it is already capable of causing severe disease and even death among humans. Scientists fear that if the virus were also to gain the ability to infect humans easily, a pandemic could result. So several countries are looking to modern methods to quickly produce a “seed strain” that is closely matched to the virus causing the pandemic (should one happen) and are also establishing production techniques based on cell cultures that can he scaled up rapidly when required.
The Novavax technology for influenza vaccines using “Virus-like particles” (VLPs) is aimed at meeting the same objectives. When viral genes are artificially introduced into cells, the proteins those genes produce can self-assemble into VLPs. These VLPs mimic the overall structure of the virus and are thereby able to evoke a strong immune response when given as a vaccine. VLPs have been produced for more than 30 different viruses that infect humans and animals, according to a review paper published in the journal Trends in Microbiology in 2003. Two vaccines against human papillomavirus types that cause cervical cancer are in advanced clinical trials and both vaccines, which use VLPs, have shown promising results.
Last year, Novavax scientists published the results of trials in which laboratory mice were vaccinated with VLPs against a H9N2 strain of bird flu. Baculovirus was used to carry key segments of three H9N2 genes into insect cells grown in culture and these cells then churned out VLPs. The baculovirus infects only some moths and therefore represents no threat to vaccinated individuals. The insect cells can be cultured with minimal risk of their harbouring mammalian germs, observes the Trends in Microbiology paper. Besides, as VLPs lack any genetic material, they cannot become infectious.
In mice, the VLPs elicited antibody levels that were similar to those produced by purified whole H9 virus vaccine and considered adequate for protection in humans, reported the Novavax scientists in their paper published in the journal Vaccine.
In response to the threat posed by the H5N1 bird fin virus, both the European Union and the U.S. have embarked on an effort to produce and test in clinical trials “pandemic-like” vaccines, according to a workshop report published by the National Academies Press. The U.S. Food and Drug Administration (FDA) recently issued its recommendations for an accelerated process to license new pandemic vaccines that could use cell technologies rather than eggs.
Clinical trials of the Novavax-technology-based pandemic influenza vaccines would be undertaken both in the U.S. and in India almost in parallel, according to Krishna Mohan, president of Bharat Biotech International. Under the comprehensive agreement with Novavax, Bharat Biotech would undertake the complete bioprocessing of the vaccine, including its bulk production, Dr Krishna Mohan told The Hindu.
Catherine Luke and Kanta Subbarao of the National Institute of Allergy and Infectious Diseases in the U.S. point out in a recent paper that vaccines based on inactivated viruses of H9N2 and H5 subtypes of bird flu were found to arouse a poor immune response in humans. The vaccines produced by Novavax and Bharat Biotech need to fare better in clinical trials.In the absence of a significant number of human cases of H5N1 flu, the efficacy of a vaccine to prevent the disease or at least limit its seriousness cannot be established, points out Richard Cash of the Harvard School of Public Health who is currently visiting India. The vaccine would therefore have to be approved for use on the basis, of just the first phase of clinical trials that look for side effects and measures the immune response. Such phase-I trials typically test the vaccine on just a few hundred volunteers. But it may only be when hundreds of thousands of people receive the vaccine, as during large-scale trials or in actual use, that its side effects become evident.
In the “Swine Flu Affair” of 1976, U.S. public health officials mistakenly believed that an outbreak involving a novel flu virus-at an Army base indicated that a pandemic could be imminent. The U.S. Government ordered a voluntary mass immunisation campaign, which was called off after several cases of Guillain-Barre syndrome, a form of paralysis that can be fatal, were detected among those vaccinated, if a vaccine were approved for use on the basis of phase-I trials alone, then its widespread use must be accompanied by close surveillance to detect side effects, Dr. Cash told The Hindu. |
