these vaccine results seem encouraging, do they not...?
would assume if world can avoid avian flu this flu season, then we ought to have adequate vaccine supply by next year? Please advise.
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August 7, 2005
By LAWRENCE K. ALTMAN The New York Times
WASHINGTON — Government scientists say they have successfully tested in people a vaccine that they believe can protect against the strain of avian influenza that is spreading in birds through Asia and Russia.
Health officials have been racing to develop a vaccine because they worry that if that strain mutated and combined with a human influenza virus to create a new virus, it could spread rapidly through the world. (The vaccine cannot lead to such a situation because it is made from killed virus.)
Tens of millions of birds have died from infection with the virus and from culling to prevent the spread of the virus. About 100 people have been infected, and about 50 have died from this strain of the avian influenza virus, called A(H5N1). So far there has been no sustained human-to-human transmission, but that is what health officials fear, because it could cause a pandemic. And that fear has driven the intense research to develop a vaccine.
The director of the National Institute of Allergy and Infectious Diseases, Dr. Anthony S. Fauci, said that while the vaccine that has undergone preliminary tests could be used on an emergency basis if a pandemic developed, it would still be several months before that vaccine is tested further and, if licensed, offered to the public.
"It's good news," Fauci said. "We have a vaccine."
But he cautioned: "We don't have all the vaccine we need to meet the possible demand. The critical issue now is. 'Can we make enough vaccine, given the well-known inability of the vaccine industry to make enough vaccine."'
An earlier human vaccine against A(H5N1) avian influenza virus was prepared after it first appeared in the world, in Hong Kong in 1997. That vaccine was never fully developed or used, and the strain has mutated since then.
In interviews over recent days, Fauci has said that tests so far have shown that the new vaccine produced a strong immune response among the small group of healthy adults under age 65 who volunteered to receive it, although the doses needed were higher than in the standard influenza vaccine offered each year. The vaccine, developed with genetic engineering techniques, is intended to protect against infection, not to treat those who are sick.
Further tests are expected to be conducted among two groups — people 65 and older, and children — over the next several months. Fauci expressed confidence that they would confirm the success of the first tests and answer remaining scientific questions.
Because the vaccine is made in chicken eggs, "a potential major stumbling block" to successful mass production is the number of eggs farmers can supply manufacturers, Fauci said.
If manufacturers can overcome such hurdles, the new vaccine could go far in averting a possible pandemic of human influenza, Fauci said.
Only a small number of human cases of A(H5N1) influenza have been found. Although a few cases may have been transmitted from person to person in Asia, the A(H5N1) strain has not garnered enough strength to spread widely among humans anywhere.
As of Friday night, according to the World Health Organization in Geneva, the avian strain has killed 57 of the 112 people it has been known to infect in four countries. They are Cambodia (four cases), Indonesia (one case), Thailand (17 cases), and Vietnam (90 cases).
The additional tests are needed in part to determine the optimal dose of vaccine; how many shots people will need for protection; and whether adding another ingredient called an adjuvant to the vaccine could raise the potency of lower doses, stretching the number of people that could be protected. Even when these tests are completed, more time will be needed before the Food and Drug Administration can license the human vaccine and before policy-makers determine the when and how it should be administered.
Government researchers and others developed the vaccine, which is produced by Sanofi-Pasteur, a French vaccine company that is now part of Aventis. The government could decide to release the product under emergency conditions if an A(H5N1) influenza pandemic struck before the testing process was completed.
Although cautioning that the vaccine has not been fully tested, Fauci said that the initial test findings have given the federal government enough confidence to start the process of adding millions more doses of the vaccine to the 2 million it has bought. The present supply is stored in bulk form, and "we cannot put it in vials until we find out what the right dose is," Fauci said.
The manufacturer needs to know the dose and regimen to determine how much more vaccine it can produce and make available to the United States and other customers.
The American vaccine is derived from a strain that Dr. Robert G. Webster helped isolate from a human case in Vietnam. He is an internationally known influenza expert at St. Jude's Children's Research Hospital in Memphis, Tenn., whose work is supported in part by Fauci's institute.
Because the A(H5N1) strain is lethal for chickens and so could not be grown in eggs, Webster had to use a recently developed technique known as reverse genetics to remove the gene that made the virus deadly. This altered seed virus was used by Sanofi-Pasteur to produce the vaccine in chicken eggs under contract from the government.
Fauci's institute received the first batch of 8,000 doses from Sanofi-Pasteur in the spring. In April, doctors injected the vaccine into 452 healthy volunteers at three centers: the University of Maryland in Baltimore; the University of Rochester in New York; and the University of California, Los Angeles.
Doctors at these centers drew blood from the volunteers to document that they had no antibody to A(H5N1) before they received the first of two injections of the vaccine. Then the doctors drew another blood sample four weeks later when the volunteer received a second injection of the vaccine.
Fauci said his team is considering drawing a fourth blood sample to measure the antibody response over a longer period. He also said that the team is considering adding a third dose of vaccine to determine the maximum response that the vaccine can elicit.
The recipients received one of four different doses of the vaccine: 7.5 micrograms per dose, 15 micrograms, 45 micrograms or 90 micrograms.
The results confirmed the scientists' prediction that a larger dose of A(H5N1) virus than used in standard influenza vaccines would be needed to produce the strongest immune responses, Fauci said.
Evidence that the vaccine could be protective came from analysis of 113 of the 452 participants in the study. These findings have been discussed only among the doctors who conducted the studies and the scientists at his institute, Fauci said.
Though the numbers were small, they were large enough to show scientifically that the vaccine elicited a strong immune reaction, a critical point of the study.
The only way scientists can prove the effectiveness of the vaccine is if an epidemic of the A(H5N1) strain occurs among people. Ethics prohibit deliberately infecting people for experimental purposes, in part because that step could lead to the kind of pandemic that scientists are trying to prevent.
Under such circumstances, scientists must show that as the dose of the vaccine is progressively increased, the immune response increases proportionately.
Fauci said he was "encouraged" about the findings because "many other experimental vaccines have produced flat dose-response curves," meaning that the vaccines were ineffective because they did not stimulate the necessary immune response.
"What confirms the fact that you have an immunologically potent vaccine is when you get a good dose-response curve, and unquestionably we got one with this vaccine," he said.
Scientists had to test the human avian influenza vaccine on volunteers because the A(H5N1) strain differs in significant ways from the conventional strains that cause human influenza.
Also, the influenza shots that are offered each year are derived from the human strains that are circulating most widely at the time experts choose the components of the next vaccine. Human influenza viruses mutate enough each year to force changes in the standard vaccines. Such vaccines produce a broader and stronger immunity because recipients build up an immunity to influenza from repeated immunizations and exposure to the influenza virus.
In a sense, the standard annual influenza shots are booster doses. But the A(H5N1) vaccine is a primary immunization because, having had no exposure to that virus, people lack any immunity to the avian strain.
The United States is thought to be the only country that has produced a human vaccine against the A(H5N1) influenza strain. Australia, Canada, France and Japan are among countries where scientists are trying to develop human avian influenza vaccines, according to the World Health Organization.
Fauci's institute also contracted with Chiron, which is based in Emeryville, Calif. to make another A(H5N1) vaccine. But tests of the Chiron vaccine have not started because of delays related to prior contamination found in Chiron's plants.
Fauci said his institute has 8,000 doses of the Chiron human A(H5N1) vaccine and hopes to start testing it in volunteers in late fall. The tests will follow the same steps taken with the Sanofi-Pasteur vaccine, he said.
NYT-08-06-05 1330EDT
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