Study: Adjuvanted H1N1 vaccine was very effective

May 7, 2010 (CIDRAP News) – A preliminary study from Germany suggests that an adjuvanted vaccine against the pandemic H1N1 virus was highly effective in adolescents and younger adults and moderately effective in older people, according to a report published yesterday in Eurosurveillance.

Using data on vaccinated and unvaccinated people who had confirmed cases of H1N1 and survey data on vaccination coverage, a team from the Robert Koch Institute in Berlin estimated vaccine effectiveness (VE) in people aged 14 through 59 years at almost 97%. VE in those 60 and older was estimated at about 83%.

By comparison, seasonal flu vaccines well-matched to circulating strains are generally said to be about 70% to 90% effective in healthy young adults, but effectiveness in the elderly is probably substantially lower.

The researchers write that their findings may overestimate VE to some degree, because vaccinated people might have been less likely to be tested for H1N1 if they got sick. But they say the results still suggest excellent effectiveness for the vaccine.

Their study is among the first to try to assess how well an H1N1 vaccine actually protected people during the pandemic. Studies conducted before licensing of H1N1 vaccines last year examined the antibody responses they generated in volunteers but did not assess how well they protected people from actual illness.

Almost all Germans who were vaccinated against H1N1 received GlaxoSmithKline's Pandemrix, which contains 3.25 micrograms (mcg) of antigen plus the proprietary adjuvant AS03, the Eurosurveillance report notes. On the basis of immunogenicity trials, German authorities concluded that one dose of the vaccine was sufficient. The Koch team sought to determine whether the single-dose regimen was protective.

(H1N1 vaccines used in the United States contain no adjuvants and carry a higher dose of antigen—15 mcg, the same amount as in seasonal flu vaccines.)

All confirmed pandemic H1N1 cases in Germany were required to be reported, and public health officials interviewed patients to find out about chronic health conditions, hospitalization, and flu vaccination status. Because studies show that most people develop antibodies within 14 days after getting a seasonal flu shot, the researchers defined vaccine failure as confirmed pandemic flu in a person who was vaccinated more than 14 days before getting sick.

The team assessed possible risk factors for vaccine failure by comparing those patients with those who got sick with H1N1 within 7 days after vaccination (before immunity could develop), as that group was considered to represent vaccinated people in general.

Over a 10-week period starting in mid November, about 71,000 Germans had confirmed cases of pandemic flu. Among 45,733 cases for which information was available, 425 patients (0.93%) had been vaccinated, including 180 who were vaccinated with 7 days before illness, 48 vaccinated 8 to 14 days before illness, and 61 vaccinated more than 14 days before illness.

Overall vaccine coverage in Germans 14 and older was estimated at 6.8% (95% confidence interval [CI], 5.0% to 9.2%). That was based on a telephone survey in which a randomly selected sample of 1,000 people were interviewed every 2 weeks, starting about 3 weeks after the vaccination drive began in late October.

Combining these findings, the authors calculated that the vaccine's effectiveness in people 14 to 59 years old was 96.8% (95% CI, 95.2% to 97.9%) and that VE in older people was 83.3% (95% CI, 71.0 % to 90.5%).

In an initial (univariate) analysis, only two variables emerged as risk factors for vaccine failure: age over 60 and previous seasonal flu vaccination. Further statistical analysis showed that older age was the only factor independently associated with vaccine failure (odds ratio, 1.82; 95% CI, 1.03 to 3.21). Underlying chronic disease and hospitalization were not significantly associated with vaccine failure.

The report says the higher VE in younger people is in keeping with findings about the effectiveness of seasonal flu vaccines. A recent review put the effectiveness of seasonal flu vaccines at up to 80% in younger adults in seasons when the vaccine matched circulating flu strains, it notes, whereas studies have shown low or uncertain effectiveness in the elderly.

Although the VE was lower in older adults, the results suggest that the AS03-adjuvanted vaccine offers "acceptable" protection of the elderly from confirmed H1N1 illness, but this needs further confirmation, the authors add.

They cite one limitation of their study: Vaccinated patients with flu-like illness might have been less likely to be tested for H1N1 than unvaccinated patients, potentially leading to an overestimate of VE. "Thus, our results must be regarded as an upper limit estimate. They nevertheless suggest excellent VE of the AS03-adjuvanted pandemic vaccine after one dose with lower but still acceptable VE in elderly persons."

Lisa Jackson, MD, MPH, an immunization researcher and senior investigator at the Group Health Research Institute in Seattle, called the study interesting but said she is a little skeptical of the VE estimates.

A major strength of the study is its use of lab-confirmed flu cases, she commented by e-mail. But its limitations, she said, include uncertainty about the timing of disease onset after vaccination and "likely inaccuracy in estimating population vaccine coverage, which is critical to this type of analysis. Estimating vaccine coverage was inherently difficult given the fast pace of the vaccination campaign and further limited by the use of a relatively small sample (N=1,000) to estimate coverage."

Jackson said the VE estimates "are substantially higher than normally reported for seasonal flu vaccine in randomized studies conducted under much more controlled circumstances, so I'm a bit skeptical of those numbers. It is true, though, that AS03 is a very good adjuvant and so I don't doubt that such a vaccine could work."

She also found it interesting that previous seasonal flu vaccination was associated with a lower estimate of VE in the univariate analysis. This could be due to bias, but it recalls the recent Canadian studies suggesting that seasonal flu vaccination was associated with a higher risk of H1N1 disease, "so it is intriguing," she said. (The Canadian findings have not been duplicated elsewhere.)

Wichmann O, Stocker P, Poggensee G, et al. Pandemic influenza A(H1N1) 2009 breakthrough infections and estimates of vaccine effectiveness in Germany 2009-2010. Eurosurveillance 2010 May 6;15(18) [Full text]

See also:

Apr 6 CIDRAP News story "New Canadian studies suggest seasonal flu shot increased H1N1 risk"

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