News Summary

• There are critical gaps in our understanding of the effectiveness of licensed influenza vaccines in the United States.
• Contrary to previously-established estimates of 70–90 percent effectiveness in protecting healthy adults against influenza when the seasonal vaccines are well matched to the circulating strains, the new analysis reports only 59 percent efficacy by the type of vaccine used to inoculate 90% of United States citizens.
• Dr. Michael Osterholm and colleagues from CIDRAP, the Marshfield Clinic Research Foundation and Johns Hopkins University screened 5,707 medical articles published between 1967 and 2011 for studies of randomized controlled trials and observational studies assessing the reduction in influenza risk after vaccination with licensed vaccines.

Quotes

• ”Current protection is not adequate for a pandemic setting where antigen match is ideal and antigen drift has not occurred. The difference between 69 percent effectiveness and 90 percent effectiveness will have a major public health effect in any pandemic that causes serious morbidity or increased mortality.” - The study's authors. 
• “The ongoing public health burden caused by seasonal influenza and the potential global impact of a severe pandemic really signals the urgent need for a new generation of highly effective and cross-protective vaccines that we can produce rapidly. We have new vaccines in development now based on novel antigens which could be more effective than current vaccines. Active partnerships between industry and government could accelerate research and reduce regulatory barriers.” - Michael T. Osterholm, Ph.D., M.P.H. 

Full Text

There are critical gaps in our understanding of the effectiveness of licensed influenza vaccines in the United States, according to a comprehensive study lead by the Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota. The study is published in the November edition of The Lancet Infectious Diseases, (published online October 25, 2011.)

Dr. Michael Osterholm and colleagues from CIDRAP, the Marshfield Clinic Research Foundation and Johns Hopkins University screened 5,707 medical articles published between 1967 and 2011 for studies of randomized controlled trials and observational studies assessing the reduction in influenza risk after vaccination with licensed vaccines.

Including only those studies that used sensitive and highly specific diagnostic tests to confirm influenza, the authors identified 31 eligible studies that yield the most reliable information on the effectiveness of current influenza vaccines. The analysis included studies published from 1967 to February 2011.

Randomized controlled trials of trivalent inactivated vaccines (TIV) were effective in preventing influenza in eight of twelve (67%) seasons and had a combined efficacy of 59 percent against influenza in healthy adults.

The live attenuated influenza vaccine (LAIV) was shown to provide significant protection in nine (75%) of twelve seasons against infection and had a combined efficacy of 83 percent against influenza in children aged 6 months to 7 years.

None of the LAIV studies showed significant protection in healthy adults 59 years of age and younger. There were no studies of TIV and one study of LAIV showing protection for those 60 years of age and older.

The median effectiveness of the monovalent pandemic vaccine was 69 percent against medically attended pH1N1 influenza in people aged less than 65 years.

”Current protection is not adequate for a pandemic setting where antigen match is ideal and antigen drift has not occurred,” said the study’s authors. “The difference between 69 percent effectiveness and 90 percent effectiveness will have a major public health effect in any pandemic that causes serious morbidity or increased mortality.”

The study of LAIV in children 6 months to 7 years of age did find a combined efficacy of 83% in all eight seasons analyzed in 6 different randomized controlled trials. There were no randomized controlled trials of TIV for children 2 to 17 years of age meeting the study inclusion criteria.

One study assessing TIV vaccine efficacy in children aged 6 months to 2 years of age was done over two seasons with good matches between vaccine and circulating virus strains in both years. In the first year vaccine efficacy was 66%. In the second year, there were few cases and efficacy was absent. LAIV is currently licensed in the US for non-pregnant persons 2 to 59 years of age, but has not been preferentially recommended over TIV in children 2-7 years old.

The authors conclude that present vaccines are the best interventions available for seasonal influenza, but that consistent, high-level protection eludes the present generation of vaccines, especially in individuals at risk of medical complications or those aged older than 65 years.

According to the study’s authors, the latest findings should be a clarion call for more effective influenza vaccines. “The ongoing public health burden caused by seasonal influenza and the potential global impact of a severe pandemic really signals the urgent need for a new generation of highly effective and cross-protective vaccines that we can produce rapidly,” said Osterholm. “We have new vaccines in development now based on novel antigens which could be more effective than current vaccines. Active partnerships between industry and government could accelerate research and reduce regulatory barriers.”

The study’s authors include Michael Osterholm, Ph.D., M.P.H., University of Minnesota; Nicholas Kelley, Ph.D., University of Minnesota; Alfred Sommer, M.D., M.H.S., Johns Hopkins School of Public Health; and Edward Belongia, M.D., Marshfield Clinic Research Foundation.

For the full article and commentary visit: http://press.thelancet.com/tlidflu.pdf

For an embargoed podcast interview with the lead author visit: http://press.thelancet.com/fluvaccine.mp3