TORONTO - A live-virus flu vaccine applied in a nasal spray rather than an injection doesn't appear to be as effective as the standard flu shot in adults, a large U.S. study suggests.
The work, published electronically Monday by the Journal of the American Medical Association, adds to what experts believe is a growing body of evidence that live vaccine works best in children and adolescents whose immune systems haven't yet built up flu defences through years of exposures to influenza viruses or vaccines.
"There is, I think, a general sense -- and it's probably true -- that because the live vaccine has to replicate in order to induce an immune response (in the recipient), it becomes progressively less effective as you start dealing with populations that have greater and greater amounts of baseline immunity," flu vaccine expert Dr. John Treanor said in an interview.
Treanor, who is chief of the infectious diseases division of the University of Rochester (N.Y.) Medical Center, was not involved in the study.
"It's very good in young children. There's no question about it," concurred Dr. Arnold Monto, an influenza expert at the University of Michigan who is part of an unrelated multi-year study looking at the efficacy of the live-virus vaccine in adults.
So far only preliminary results of Monto's study have been published. But he was not surprised by these findings.
"I think what is interesting about the whole discussion is that the authors come to a very similar conclusion to the one we have," he said.
"And that is that there is a problem in using the live-attenuated (weakened) vaccine in a population which has immunity to influenza. Because in order to make the vaccine work you have to infect the individual."
The live-virus vaccine works by infecting the recipient with a virus that has been weakened to prevent it from causing illness. A number of experts believe that attenuation process, which is essentially to make the vaccine safe to use, may make it too weak for adults.
The pharmaceutical manufacturer that makes the vaccine, MedImmune, does not share that view.
MedImmune, which is based in Gaithersburg, Md, insisted Monday that there is little head-to-head evidence comparing adult responses to their vaccine, FluMist and standard flu shots, which are made from killed flu viruses.
And the studies that have been done show a mixed picture, said Dr. Chris Ambrose, MedImmune's director of medical affairs.
"I think this study is another study that adds to the list of studies, which is good. But basically, we think that there's more research that needs to be done in the adult population," Ambrose said.
FluMist is not currently licensed in Canada, though the company is contemplating entry into this market.
"We have not filed yet in Canada but we are actively evaluating it right now," Ambrose said.
Earlier this year MedImmune submitted a marketing authorization application to the European Medicines Agency.
This study, done by researchers from the U.S. Armed Forces Health Surveillance Center and the Jackson Foundation for the Advancement of Military Medicine, looked for hospitalizations for influenza or pneumonia -- influenza can lead to pneumonia -- in military personnel over three flu seasons.
They compared rates of the illnesses in service people who had received flu shots, FluMist and those who didn't take either protective option.
In all three years, the troops who received a flu shot were less likely to need health care for influenza than those who got the live-virus vaccine.
And in all three years those who received the live-virus spray vaccine were more likely to be hospitalized for pneumonia and influenza than either those who received the killed-virus shot or those who remained unimmunized.
The study was not a randomized controlled trial, where people are randomly assigned to receive one or another treatment or no treatment. The evidence produced by that kind of study is considered the strongest form of proof medical trials can generate.
And there were other limitations. The authors didn't have detailed information on the participants -- they didn't know who smoked, for instance. And they didn't have virological test results that confirmed cases put down as influenza were actually influenza.
But there were strengths as well, most notably the enormous numbers involved. For each of the three years they had access to the records of over one million armed forces personnel.
The outcomes varied a bit from year to year, as you would expect with influenza. Some years flu hits harder than others. Some years the flu shot is a poor match to the circulating flu strains, which actually gives the nasal spray vaccine an advantage. The live-virus vaccine is thought to give more cross-protection than the shot.
Dr. Frederick Hayden, an influenza expert at the University of Virginia, said the findings show the issue needs further study.
"It's certainly of sufficient concern in my view that this needs to be looked at more carefully going forward with regard to the relative efficacy," he said.
"It just adds to this body of evidence to raise the concern that it may not be optimally immunogenic in an (immunogenically) experienced adult population."
