Even saving just a couple weeks or so could make a difference, some experts said. "If the H1N1 vaccine had been available in quantity 1 month earlier, it would have made a difference in containing the [2009] pandemic," said Dr. W. Paul Glezen, a professor of molecular virology and microbiology at Baylor College of Medicine, Houston. "Using a tissue culture substrate to grow influenza viruses provides flexibility to vaccine production not available before using embryonated eggs. It should be safer as well, with less danger of contamination. Holly Springs is the beginning, and a good start. Most of the other manufacturers are also developing facilities for growing vaccine in tissue culture. The evidence suggests that all influenza vaccine should be produced in mammalian cells because adapting human influenza virus to grow in eggs alters important antigens that may result in vaccine that is less effective. The shorter production time also means the decision for [seasonal] vaccine constituents can be delayed to allow more time to assess the emergence of new variants to include in the vaccine."
"One month less" time to produce pandemic vaccine "is probably the best-case scenario. We might not get a full month, but it is supposed to be somewhat faster" than egg-based production, said Dr. Schaffner. "It could get the program going quicker, it could give the public a measure of confidence that the response is speedy and more optimistic. In 2009, it was perceived that the government over-promised and under-delivered. If we can start getting vaccine into the pipeline quicker, the public will think [the public health response] is on the ball."
But the reality may be more sobering. A Novartis cell-culture plant in Europe made H1N1 pandemic vaccine in 2009 that did not arrive any quicker than egg-based vaccine, Dr. Osterholm noted. Even if the 2009 European vaccine had glitches that could be avoided in America when the next flu pandemic strikes, what difference might a few weeks make for public health? "It means that vaccine would arrive at about the peak of the second [infection] wave, which is still really late," he said. "Even if you shaved a month off in 2009, it still would have had a limited impact. We need to do our best to have vaccine before the second wave."
Dr. Robinson agreed that even faster would be better. Next on the agenda for the Biomedical Advanced Research and Development Authority and HHS is to finish plans to make pandemic flu vaccine using recombinant technology. Dr. Robinson said this could produce vaccine within about 12 weeks, and that this capability is roughly 2 years away.
But recombinant vaccine may not be ideal either. Investigational recombinant vaccines have had effectiveness levels comparable to the 60% seen in trivalent inactivated vaccines. The answer, Dr. Osterholm said, lies in better understanding the immunity produced by natural flu infection and using that as a model to develop new vaccine antigens that reach much higher levels of effectiveness.
"Much of what we know about flu immunity is for hemagglutinin, and that’s not much," he said. "In 2009, there was clear evidence that 65- to 70-year-olds had residual protection to H1N1 from when that virus last circulated in the 1950s. These elderly people were entering immunosenescence, but they still had good protection. Yet we can’t get good protection from year to year with hemagglutinin-based vaccines. That shows something else going on immunologically that we should think about. Several possible target antigens have been identified, but so far they are not going anywhere because there has not been sufficient investment.
"Novel antigens are the ultimate flu vaccine goal. Is the Holly Springs plant a good thing for the short term? Sure, it’s an incremental increase in preparedness. But it’s not a major change in preparedness," Dr. Osterholm said.
Dr. Osterholm and Dr. Robinson said that they had no disclosures. Dr. Schaffner said that he has been a consultant to GlaxoSmithKline, Dynavax, Novartis, and Pfizer, and that he has served on data safety and monitoring boards for Sanofi-Pasteur and Merck. Dr. Glezen said that he has received a research grant from MedImmune.