Current trivalent flu vaccine lacks efficacy; improved flu vaccine needed

Osterholm MT. Lancet Infect Dis. 2011;doi:10.1016/S1473-3099(11)70295-X.

Significant evidence of efficacy is lacking for the current licensed influenza vaccines in the US, and better vaccines are needed to provide adequate protection, according to results of a new study.

According to the researchers, led by Michael Osterholm, PhD, of the University of Minnesota, influenza vaccines can provide moderate protection against confirmed influenza, but protection is often reduced or absent, and evidence for protection in adults aged 65 years or older is lacking. In contrast, previous studies have shown that live-attenuated influenza vaccines consistently show highest efficacy in young children (aged 6 months to 7 years), but the Advisory Committee on Immunization Practices does not recommend LAIV over trivalent inactivated vaccine in these children.

“Evidence for consistent high-level protection is elusive for the present generation of vaccines, especially in individuals at risk of medical complications or those aged 65 years or older. The ongoing health burden caused by seasonal influenza and the potential global effect of a severe pandemic suggests an urgent need for a new generation of more highly effective and cross-protective vaccines that can be manufactured rapidly,” Osterholm said in a press release.

However, he said public support should be maintained for current vaccines because they are the best intervention available for seasonal influenza.

According to the study published online in The Lancet Infectious Diseases, there are no published meta-analyses that have assessed efficacy and effectiveness of licensed US influenza vaccines with sensitive and highly specific diagnostic tests to confirm influenza. Therefore, the researchers searched Medline for randomized controlled trials that assessed a relative reduction in influenza risk of all circulating influenza viruses during individual seasons after vaccination and observational studies met inclusion criteria.

Osterholm and colleagues reviewed eligible articles that were published from 1967 to Feb. 15, 2011, and used reverse transcription polymerase chain reaction or culture to confirm influenza. A total of 5,707 articles were screened, and 31 studies were identified (17 randomized controlled trials and 14 observational studies).

Efficacy of TIV was shown in eight (67%) of the 12 seasons analyzed in 10 randomized controlled trials (pooled efficacy=59% [95% CI, 51-67] in adults aged 18 to 65 years), but no such trials met inclusion criteria for children aged 2 to 17 years or adults aged 65 years or older.

Efficacy of LAIV was shown in nine (75%) of the 12 seasons analyzed in 10 randomized controlled trials (pooled efficacy=83%; 95% CI, 69-91) in children aged 6 months to 7 years, but no such trials met inclusion criteria for children aged 8 to 17 years. Vaccine effectiveness was variable for seasonal influenza: six (35%) of 17 analyses in nine studies showed significant protection against medically attended influenza in the outpatient or inpatient setting.

Median monovalent pandemic H1N1 vaccine effectiveness in five observational studies was 69% (range, 60-93).

The researchers concluded that this amount of protection is inadequate in a pandemic when the antigen match is ideal and antigen drift has not occurred: “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,” they said in the press release.

James M. Hughes

Influenza is a particularly challenging emerging infectious disease that defies predictions and causes serious morbidity and mortality in groups at highest risk for complications (eg, the very young, the elderly, pregnant women) at rates that vary from year to year. In addition, the threat of another influenza pandemic is constantly with us. Seasonal influenza vaccines which are reformulated each year are the cornerstone of influenza prevention and control. In a carefully done, systematic review and meta-analysis of the literature, Michael Osterholm and colleagues identified 31 peer-reviewed studies (17 randomized controlled trials and 14 observational studies) that used rigorous diagnostic endpoints of virus culture or RT-PCR to assess influenza vaccine efficacy or effectiveness. They confirm that protection from the vaccine varies from year to year, that these studies did not include subjects 65 years of age and older, and that improved influenza vaccines are needed. In the meantime, they recommend use of current vaccines as the best tools currently available to control annual epidemics.

It is important that aggressive efforts to improve coverage of the population, especially groups at high risk for complications and health care workers, continue. In addition, it is important to emphasize the importance of personal behaviors including proper respiratory etiquette and cough hygiene, hand hygiene, and staying home from school or work while ill with an acute respiratory infection.

The results of this analysis should also provide additional motivation to continue to strengthen national and global influenza surveillance and for government, academia and industry to cooperate to develop improved rapid influenza diagnostics and alternative technologies for more timely production of both seasonal and pandemic vaccines and ultimately for production of a universal influenza vaccine.

James M. Hughes, MD
Infectious Diseases Society of America Editorial Board Member
Immediate Past-President

Disclosure: Dr. Hughes reports no relevant financial disclosures.

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