NIH Study Identifies Better Parameter to Predict Flu Vaccine Effectiveness

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Traditional methods of measuring the effectiveness of vaccines against the flu are called into question by new findings from the NIH.

Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), a branch of the National Institutes of Health (NIH), have concluded that an antigen other than the one that is typically used for the creation of flu vaccines may be a more effective target for the prevention of infection. Although most current seasonal vaccines attempt to induce the creation of antibodies against the flu cell-surface protein hemagglutinin, researchers from NIH found that neuraminidase (NA) may actually be a better flu cell-surface protein to target. NA is an enzyme that allows the flu virus to exit host cells so it can further replicate in the body. Measuring antibodies to NA may be a better indicator of protection against influenza infection, the researchers hypothesized.

In the publication mBio, NIH researchers wrote that recent poor performance of seasonal flu vaccines prompted them to investigate other “immunological correlates of protection” besides the hemagglutinin antigen. Sixty-five healthy volunteers were intranasally inoculated with a wild-type 2009 A (H1N1) pandemic influenza A challenge virus at the NIH Clinical Center. Researchers measured hemagglutinin inhibition (HAI) titer and found that although a higher HAI conferred some protection against the flu (i.e., symptoms were not as severe), neuraminidase inhibition (NAI) titer was a better predictor of overall flu reduction.

The range for titers of HAI defined as "protective" was originally established in 1972 by Hobson et al. via a live influenza virus challenge, according to the mBio piece. In that study, an HAI of 18 to 36 was found to be associated with 50% protection from infection. Since then, say the researchers, newer epidemiological studies of vaccine performance measuring HAI have shown that this range is associated with less protection than originally thought-and a titer of HAI within the protective range "would not necessarily include the prevention of a clinical influenza-like illness, even if it does predict some reduction in the duration of illness and viral shedding, and thus spread of disease." During the past 10 years, vaccines have had an overall mean effectiveness rate of 40%, they wrote.

Ultimately, the researchers concluded that NAI titer is a stronger correlate of disease severity than is HAI titer alone, and individuals with high titers of NAI experienced less severe/fewer symptoms and a shorter duration of viral shedding. “This challenge study confirms the importance of NAI titer as a correlate and for the first time establishes that it can be an independent predictor of reduction of all aspects of influenza disease,” the study authors wrote. “This suggests that NAI titer may play a more significant role than previously thought and that neuraminidase immunity should be considered when studying susceptibility after vaccination and as a critical target in future influenza vaccine platforms.” The researchers admitted that HAI and NAI titers, measured together, may even be a better predictor of disease than either titer measured alone.


Evolving viral phenotypes have also contributed to diminishing effectiveness of seasonal flu vaccines. In fact, in late 2015, the Committee on Energy and Commerce concluded that the 2014–2015 vaccine did not defend against the dominant H3 A strain of influenza because the virus mutated after vaccine production was already well underway. The antigenic drift meant the 2014–2015 vaccine’s mean overall effectiveness rate was just 19% (later updated to 23%)-the lowest effectiveness rate that has been recorded during the past 10 years.

Sources: NIH, mBio