Thursday, June 12, 2008

NEJM : Baxter's Cell Cultured Vaccine



# 2063



It is generally agreed that having an effective vaccine, in quantity, is the best way to combat an influenza pandemic.  Even though vaccines don't confer 100% immunity, if enough of the population has immunity, it can effectively starve a virus of susceptible hosts and hopefully the pandemic will fade away.


Pandemic vaccines are problematic, however. 


First, a targeted vaccine cannot be produced until a pandemic strain is identified, and using our current egg-based technology, it can take another 20-28 weeks to produce the first batches of vaccine. 


Second, our global capacity for creating vaccines using this egg-based technology is limited.   No one knows exactly how much we could produce in a year, but estimates are that only enough vaccine could be produced to inoculate 10%-15% of the world's population.


There are other problems, of course.   Distribution of vaccines, particularly during a pandemic, could be very difficult.    Having a vaccine at the manufacturing facility is only half the battle.


But the big bottleneck has been our egg-based manufacturing technology, and the holy grail of vaccine manufacturers has been the development of a cell-culture vaccine.



Yesterday the NEJM (New England Journal of Medicine) published two articles on Baxter International's cell-cultured vaccine, sparking an avalanche of media coverage.  


The primary study may be read here.



A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture


Hartmut J. Ehrlich, M.D., Markus Müller, M.D., Helen M.L. Oh, M.D., Paul A. Tambyah, M.B., B.S., Christian Joukhadar, M.D., Emanuele Montomoli, Ph.D., Dale Fisher, F.R.A.C.P., Greg Berezuk, M.S., Sandor Fritsch, Ph.D., Alexandra Löw-Baselli, Ph.D., Nina Vartian, Ph.D., Roman Bobrovsky, Ph.D., Borislava G. Pavlova, Ph.D., Eva Maria Pöllabauer, M.D., Otfried Kistner, Ph.D., P. Noel Barrett, Ph.D., for the Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team





Here is how Reuters covered the story.





Monkey cells used for bird flu vaccine


June 12, 2008

WASHINGTON: A bird flu vaccine made from monkey cells instead of chicken eggs has been reported effective by corporate researchers.


The researchers, from drug company Baxter International, documented the use of monkey cells as a safe alternative for influenza vaccinations.


“Cell culture technology could represent the future of influenza vaccine production,” said virologist John Oxford of The Queen Mary School of Medicine in London.


Scientists had previously been using chicken eggs but they found it difficult to obtain the right type and observed that the virus, H5N1, kills chickens rapidly.


The trial, carried out on more than 250 people and reported in the New England Journal of Medicine, showed the vaccine produced a strong immune response in people who received two doses.





Admittedly, this sounds promising.   But it is a little soon to start popping Champaign corks.



In a perspective article appearing in this month's NEJM entitled  Vaccine Preparedness — Are We Ready for the Next Influenza Pandemic?  by Peter F. Wright, M.D., we are cautioned that while cell-culture technology may one day greatly increase our ability to produce vaccines,  that we aren't there yet.


Dr Wright writes:


Are we prepared for pandemic influenza?  We are not ready to put a vaccine in the field should H5 gain person-to-person transmissibility or should another strain emerge. The work on novel vaccine approaches, however, suggests that we may still make it, if influenza continues to stay in its lair and largely confine itself to avian hosts.




The conversion from egg-based manufacturing to cell-culture manufacturing will require expensive conversions of vaccine plants and will take time.  We are still years away from seeing this new technology in widespread use.



Experts have cautioned that Baxter International used a different, and lower, standard for determining whether a vaccine conferred immunity than is normally used in the industry (see Helen Branswell's excellent coverage).   This may have artificially raised the response rate, although Dr. Hartmut Ehrlich, lead author on the study, expressed confidence in this benchmark.



The Baxter vaccine also uses a whole unmodified virus (killed in the manufacturing process), instead of a split virus.  While this is believed to produce a more robust immune response, it can also result in more adverse reactions.  



The most common reactions reported among the 275 people in the Baxter study were injection site swelling and soreness and headache. 



Another drawback is that the whole virus must be grown in a biosafety level III  laboratory.   Normally, we use a `split' virus, containing only part of the genetic material of a virus, rendering it `safer' to handle.   



Dr.  Wright in his perspective article points out that we've used whole, live polioviruses for many years to produce inactivated polio vaccine, and have done so without incident.    Still, proper biocontainment at the manufacturing site will be an issue.



The bottom line is: This is a step forward, perhaps even a big step. 


But it will probably take years, and a substantial financial commitment by the world's vaccine manufacturers to translate this research into a global capacity to rapidly produce large quantities of cell-cultured vaccine.