Researchers who analyzed published literature found the type of flu shots used to inoculate 90% of Americans would only protect about 59% of the population, which is in stark contrast to established estimates of 70-90% effectiveness when there is a good match of vaccine to circulating strains. They said there are critical gaps in scientific understanding of the effectiveness of licensed influenza vaccines in the United States, and there is a need for new vaccines in order to further reduce flu-related illness and deaths.

Writing in the 25 October online issue of The Lancet Infectious Diseases, Dr. Michael Osterholm and colleagues from CIDRAP, the Marshfield Clinic Research Foundation and Johns Hopkins University, describe how they looked through scientific papers published between 1967 and 2011 for reports of randomized controlled trials and observational studies assessing the reduction in influenza risk after vaccination with licensed vaccines.

They were interested in finding evidence of efficacy and effectiveness. Efficacy, or the extent to which a drug does what it is supposed to do in a controlled setting, is normally assessed with randomized controlled trials, while effectiveness, which is how the drug actually works in the clinical setting (some might say “in the real world”), is assessed with studies that observe how the drugs behave in representative samples of the target population.

The researchers only included in their analysis studies that used sensitive and highly specific diagnostic tests to confirm influenza (RT-PCR or culture), and they excluded some on the basis of study design and vaccine characteristics.

Altogether they screened 5,707 articles and identified 31 eligible studies (17 randomized controlled trials and 14 observational studies) of trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV).

The results showed that:

  • 10 randomized controlled trials showed efficacy of TIV in 8 out of 12 seasons (67%), with a pooled efficacy of 59% in adults aged 18-65.

  • No such trials for children aged 2 to 17 or adults aged 65 and over met the researchers’ inclusion criteria.

  • 10 randomized controlled trials showed efficacy of LAIV in 9 out of 12 seasons (75%), with a pooled efficacy of 83% in children aged 6 months to 7 years.

  • No such trials met inclusion criteria for children aged 8 to 17.

  • Vaccine effectiveness was variable for seasonal flu: 6 out of 17 (35%) analyses in 9 studies “showed significant protection against medically attended influenza in the outpatient or inpatient setting”.

  • The effectiveness of median monovalent pandemic H1N1 vaccine was 69%, calculated from pooling data from 5 observational studies covering people under the age of 65.

The researchers also noted that none of the LAIV studies showed signficant protection in healthy adults under 60 years of age, and there were no studies of TIV and only one of LAIV showing protection for those above this age.

The authors concluded that current vaccines are the best method we have available against seasonal influenza, but they don’t offer consistent, high-level protection, especially for people at risk of medical complications or those aged 65 and over.

“Current protection is not adequate for a pandemic setting where antigen match is ideal and antigen drift has not occurred,” they comment in a press statement, adding that:

“The difference between 69% effectiveness and 90% effectiveness will have a major public health effect in any pandemic that causes serious morbidity or increased mortality.”

Osterholm says:

“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.”

He said there are new vaccines being developed that are based on new antigens, and these could be more effective that the ones currently used.

He calls for “active partnerships between industry and government” to speed up research and “reduce regulatory barriers”.

Written by Catharine Paddock PhD