Shot beats nasal spray in adult seasonal flu vaccine trial

Sep 29, 2009 (CIDRAP News) – While there is evidence that the live nasal-spray vaccine for seasonal influenza works better than injectable vaccine in children, the injectable vaccine was found to be more effective in a trial in close to 2,000 young adults, according to a recent report in the New England Journal of Medicine.

Researchers led by Arnold Monto of the University of Michigan report that trivalent influenza vaccine (TIV, the injectable vaccine) was 68% effective and the live attenuated vaccine (LAIV) was 36% effective in preventing lab-confirmed flu in the study volunteers during the 2007-08 flu season.

The US government has ordered supplies of both injectable and intranasal vaccines against the pandemic H1N1 virus. Most of the supply will be the injectable form, but many of the first doses, expected to reach providers next week, will be the nasal-spray type.

Study showed 50% better protection for shot
The study was part of a 4-year randomized trial that began in 2004. The team recruited 1,952 volunteers between the ages of 18 and 49 for the study in the fall of 2007 (FluMist is currently approved for ages 2 through 49). The study took place on four university campuses in Michigan, and the mean age of the participants was 23.3 years.

The volunteers were randomly assigned to a TIV group, an LAIV group, or one of two corresponding placebo groups, with the vaccine groups five times as large as the placebo groups. About 62% of the volunteers were women, and 37.5% had received a flu shot at some time in the past.

Sanofi Pasteur provided the injectable vaccine, Fluzone, for the trial, while MedImmune provided FluMist. Several of the authors report having received grant support or lecture fees from Sanofi Pasteur.

One hundred nineteen volunteers (6.1%) had a case of lab-confirmed flu during the 2007-08 season, the report says. Of the 119 cases, 108 were A/H3N2, 1 was A/H1N1, and 11 were influenza B. Nationally, the season brought a fairly high rate of flu, mostly H3N2.

The absolute efficacy of the injectable vaccine against all types of flu was calculated at 68% (95% confidence interval [CI], 60% to 81%), while that of LAIV was 36% (95% CI, 0 to 59%), the report says.

In a comparison of the two vaccines, TIV was 50% more effective than LAIV, the authors calculated.

When the team looked at protection against influenza A strains only, TIV was found to be 72% effective (95% CI, 49% to 84%) and LAIV was 29% effective (95% CI, -14% to 55%).

There were too few cases of influenza B to allow a reasonable analysis, but the results suggested that neither vaccine was significantly better than placebo, the report says.

The authors write that the earlier years of their 4-year trial suggested that injectable vaccines worked better than the nasal spray form against influenza A, but the finding weren't conclusive. In contrast, "The current data provide clear evidence of significant differences between the two vaccines in providing protection against influenza A (H3N2) virus," they state. However, conclusive evidence about the two vaccines' effectiveness against type B is not yet available, they add.

Exactly why LAIV seems less effective in adults than in children is not yet clear, but it could be that live attenuated viruses are less able to infect adults because of their past exposure to similar strains of flu, the report says.

Experts add notes of caution
Lone Simonsen, PhD, a disease researcher who was not involved in the study, said the findings suggest that FluMist offered protection against influenza B, though the authors didn't find a significant effect. Simonsen is a research professor and research director in the Department of Global Health at George Washington University.

"The LAIV vaccine appeared to protect adults well against influenza B (vaccine effectiveness = 90%) in this study, albeit with borderline significance—probably explained by low circulation of influenza B in the study season," she said by e-mail.

The study shows there was 1 case of influenza B among 814 LAIV recipients, versus 4 cases among 325 volunteers in the combined placebo groups. That translated into a relative risk for flu of 0.10 in the LAIV group, with a 95% CI of 0.00 to 1.01. (For TIV recipients, there were 6 type B cases among 813 subjects, indicating a relative risk of 0.60 and a 95% CI of 0.14 to 2.89.)

Simonsen also commented that other clinical trials have found LAIV to be more effective than TIV in children, with better cross-protection against different strains and longer lasting effects. (The authors also mention those findings in their report.)

"It will be interesting to see what the experience with the two pandemic vaccine formulations will be this autumn—[it's] difficult to say for sure whether LAIV or TIV will be more protective in adults," she added.

Thomas Frieden, MD, director of the Centers for Disease Control and Prevention, recently cautioned against reading too much into the study. Speaking at a Sep 25 news conference on H1N1 developments, he said, "A very carefully done study in the New England Journal of Medicine showed that for one particular mix of FluMist and one particular season of flu, that FluMist was a little less effective than the flu shot.

"There are other scientific studies that suggest that for children, for example, the FluMist is a little more effective than the flu shot," he added. "And for this flu season, with this [H1N1] flu vaccine, all bets are off in terms of which is better."

Monto AS, Ohmit SE, Petrie JG, et al. Comaprative efficacy of inactivated and live attenuated influenza virus. N Engl J Med 2009 Sep 24;36(13):1260-7 [Full text]

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