The alternative, nasal-spray vaccine is made using a live virus. It too is grown in eggs, but at lower and lower temperatures, weakening or "attenuating" it so that it can survive only in the nose, not at greater body heats in the lungs.
"The nasal vaccine infects the mucosal cells (in the nose), which are closely monitored by our immune system," said Patrick Wilson, a University of Chicago immunologist. Once that system detects the vaccine, Wilson said, it produces permanent immunity to the targeted flu virus.
The first testing of both vaccines was performed on 3,000 volunteer recipients in eight laboratories at Baylor University, Cincinnati Children's Hospital, Emory University, Seattle Group Health Cooperative, St. Louis University, University of Iowa, University of Maryland and Vanderbilt University.
It also is being tested on volunteers by the five companies licensed to make up to 250 million doses of the vaccine by next spring for the U.S. market — CSL Limited, Novartis Vaccines, Sanofi-Pasteur Inc., GlaxoSmithKline, and MedImmune.
"It is tested to see if it produces the level of antibody production in the blood that reaches the FDA standard," said William Schaffner, an infectious disease specialist at Vanderbilt. "It is also tested for safety in the volunteers, something I know a little bit about since I was one of the volunteers for this vaccine."
On its Web site last week, the FDA posted the contents of the vaccines produced by the five companies, including copies of the long, multipage ingredient lists included with the doses at clinics. Schaffner said that, like many everyday foods and medicines, they contain a number of vital chemical substances that could be toxic in large volume but are included in such tiny amounts that they are harmless.
"If we looked at acetyl salacylic acid, (the active ingredient) in aspirin, taken in the current dosage it is an effective product that can relieve headaches and reduce fevers. Taken by the handful, it can have serious adverse events," Schaffner said.
"So it is with vaccines. They have trace ingredients that are in the vaccine for a variety of reasons. Taken together, the vaccines have been proven safe not only in explicit clinical trials, but in demonstrated use in hundreds of millions of doses over the years."
The ingredient that anti-vaccine activists most question is thimerosal, a preservative added in trace amounts to keep vaccine in two-shot doses from deteriorating if stored while awaiting application.
Thimerosal contains ethyl mercury, and critics allege it can cause autism and other neurological disorders. But researchers say there is so little thimerosal in the vaccine that it poses no harm. Nevertheless, they have produced thimerosal-free single-shot doses that can be ordered, and say there is no thimerosal in the nasal spray.
"I continue to be amazed that people bring this issue up," said Paul Offit, a pediatrician and noted University of Pennsylvania vaccine researcher. "There have been six exhaustive studies (of a possible link between thimerosal and autism). ... They each came back with a definitive answer: no. Three other studies were done to see if thimerosal caused any signs of mercury poisoning. All three answered: No."
Others have raised concerns about "adjuvants" — compounds sometimes added to vaccines to stimulate the immune response in recipients. It is added in several European nations, but not in the U.S. Anne Schuchat, the CDC's director of immunization and respiratory diseases, said the U.S. sees no need to add them unless the virus mutates into a far deadlier form.
"Since April this flu has caused tens of thousands of hospitalizations and more than a thousand deaths," Offit said. "This is only October and influenza is a winter disease, so no telling what we are about to see.
"We should thank the Lord that we have this vaccine at this stage."