Flu Shots Outdo Nasal Spray for Drifted Influenza

ANN ARBOR, Mich., Dec. 14 -- For seasonal flu strains that were slightly different than predicted, the traditional killed-virus vaccine in 2005 was about 75% effective, while a live attenuated-virus nasal spray was less effective, researchers here found.

In a head-to-head comparison, cell-culture and PCR analysis found a 77% absolute efficacy for the inactivated vaccine against the type A virus and two types of B virus, compared with 48% efficacy for the nasal-spray vaccine, according to a report in the Dec. 14 issue of the New England Journal of Medicine.

The standard formulation of both the flu shot and the nasal spray (FluMist) included two types of the A strain and one B strain. However, in the 2004-2005 season there were two B strains and one A strain, said Suzanne Ohmit, Dr.P.H., and Arnold Monto, M.D., of the University of Michigan here, and colleagues.

Influenza activity in Michigan began in January 2005 with an antigenically drifted type A (H3N2) virus, the A/California /07/2004-like strain, and type B viruses from two lineages, the researchers said.

The randomized, double-blind, placebo controlled study of the two vaccines included 1,247 individuals, ages 18 to 46, from four Michigan communities. The patients were vaccinated prior to the 2004-2005 flu season, and the researchers used throat-swab specimens to confirm whether the influenza virus was the cause of infection.

The absolute efficacy of the inactivated vaccine against both types of virus was 77% (95% confidence interval 37 to 92) as measured by cell culture; 75% (CI, 42 to 90) measured by cell culture or identifying it by real-time PCR; and 67% (CI, 16 to 87) measured by cell culture or observing a rise in the serum antibody titer.

The absolute efficacies of the nasal-spray vaccine were 57% (CI, ?3 to 82), 48% (CI, ?7 to 74), and 30% (CI, ?57 to 67), respectively.

The difference in efficacy between the two vaccines appeared to be related mainly to the live vaccine's reduced protection against type B viruses, the researchers said.

For example, both vaccines appeared similarly effective against culture-confirmed type A (H3N2) viruses (74% for both vaccines), but the inactivated vaccine was superior for B virus infections (80% vs. only 40%), leading to an overall higher efficacy for the inactivated vaccine, the researchers reported.

Thus, the researchers said, although the nasal spray appeared to protect reasonably well against Type A viruses but poorly against Type B viruses, the study did not have the statistical power to draw conclusions from analysis of individual types of influenza.

As for adverse effects, only four serious events occurred among participants within 30 days of receipt of vaccine or placebo. Only one, hospitalization for acute pericarditis, after receiving the live attenuated vaccine, was considered possibly related to the flu shot. The three other serious events were unrelated.

Minor reactions, such as runny nose, arm soreness, cough, headache, muscle aches, were all more likely to be reported by recipients of the live attenuated-virus nasal spray than by recipients of the matching placebo.

Could these findings be generalized to other years when the circulating viruses are either more closely matched to vaccine strains or different from them, the investigators asked. A previous head-to-head comparison of an experimental bivalent live vaccine had shown that the two were equally protective against some, but not all, endpoints.

In children, the live attenuated nasal spray has consistently been proved effective against drifted strains. However, in the current study, Drs. Ohmit and Monto said that it is possible that adults had enough prior experience with influenza that the live attenuated virus may have failed to infect their nasal passages and initiate an immune response.

Because the nasal spray has been effective in children, more information is needed about its efficacy in adults in other years. Even if it is less effective than the flu shot, as the U.S. moves toward recommending universal use of flu vaccines, the intranasal route might still be an advantage.

Finally, they said, the live attenuated vaccine could be useful in a pandemic, given that the population would have no pre-existing antibodies for the virus, and one dose would be protective.

Co-author John Victor, Ph.D., reported receiving consulting fees from Wyeth, and Dr. Monto reported consulting fees from GlaxoSmithKline, MedImmune, which produces FluMist under a license with the University of Michigan, Solvay, and Novartis.

In a second NEJM study, supported by MedImmune, maker of FluMist, James King, Jr., M.D., of the University of Maryland in Baltimore, and colleagues, studied vaccination of school children with the nasal spray as a way of reducing the spread of influenza.

All told, they found that their study added to earlier observations that found "herd immunity" reduced influenza-related illnesses following the use of a live attenuated influenza vaccine in school children or other protective actions such as school closing.

This multicenter study extends these observations and demonstrates that school-based immunization against influenza directly and indirectly reduces influenza-like illness, Dr. King wrote.

The study included 11 demographically similar clusters of elementary schools in four states. One school was assigned to participate in a vaccination program (intervention school) and one or two schools that did not participate were the control schools.

During a predicted week of peak influenza activity in each state, all households with children in the intervention and control schools were surveyed for demographic characteristics, influenza vaccination, and outcomes of influenza-like illness during the previous seven days.

In all, 2,717 (47%) of the students in the intervention schools received the nasal-spray vaccine, with a second dose for some. Compared with control households, intervention households had "significantly fewer" influenza-like symptoms and outcomes, the researchers reported.

Basic findings were as follows:

• The number of reported episodes of fever, cough, plus sore throat in children and adults in intervention households was significantly lower than in control households (P

In an accompanying editorial, Keiji Fukuda, M.D., and Marie Kieny, Ph.D., of the World Health Organization in Geneva, said the findings for the use of the nasal-spray vaccine in children "strongly suggest, but do not conclusively demonstrate, that the vaccination of the children reduced the spread of influenza to their households and to other student populations."

Although not definitive, the study provides useful supporting information for discussions of whether the recommendations for influenza vaccination should integrate population-level and individual-level approaches, they said.

In the head-to-head study led by Dr. Ohmit results were similar to those an earlier study. The degree to which these findings can be generalized is uncertain, the editorialists said, because of the wide confidence intervals, and because the relative performances of the vaccines may vary according to the age of the recipient, the preexisting levels of immunity, and the specific virus.

However, they said, the findings suggest that the two types of vaccines can confer similar protection against influenza A in healthy adults. And although some have questioned whether the substantial effort to produce and deliver influenza vaccine is justified, the answer is "unambiguously, yes," they said.

In line with these conclusions, they said, the WHO recently convened international experts to help address issues related to preparedness for pandemic influenza and to develop a global pandemic plan to increase vaccine supply as well as accelerated research to develop better influenza vaccines.