Neuraminidase inhibition (NAI) titer is a better predictor of protection against influenza infection than hemagglutination inhibition (HAI) titer, according to new research, which could have implications for future flu vaccine development.

Investigators at the National Institute of Allergy and Infectious Diseases (NIAID) and the University of Pennsylvania, Philadelphia, performed a healthy volunteer challenge study with a wild-type 2009 A(H1N1)pdm influenza A challenge virus at the NIH Clinical Center in Bethesda, Md., to evaluate two groups of participants with HAI titers of greater than 1:40 and less than 1:40. The primary objective was to determine whether participants with HAI titers of greater than 1:40 were less likely to develop mild to moderate influenza disease after intranasal inoculation

In a multiple regression analysis, researchers evaluated the independent effects of both HAI and NAI titers on four diseases severity measures. In all measures – duration of shedding (HAI: P = .164; NAI: P less than .001), duration of symptoms (HAI: P = .497; NAI: P = .011), number of symptoms (HAI: P = .533; NAI: P less than .001), and symptom severity score (HAI: P = .906; NAI: P less than .001) – increasing NAI titers showed a statistically significant independent effect of decreasing severity, while HAI titers showed no significant independent effect on any of the disease severity measures examined.

When grouped by baseline NAI titers, those participants with high titers (greater than or equal to 1:40) had only minimal increases in NAI after challenge, but unlike HAI titer, every cohort with a low NAI titer had a rise in NAI titer after challenge, regardless of the outcome.

“These data further suggest that NAI titer may play a more significant role as a correlate of protection than previously thought and that the role of neuraminidase immunity should be considered when studying influenza susceptibility after vaccination and as a critical target in future influenza vaccine platforms,” Dr. Jeffery K. Taubenberger of the NIAID and his coauthors concluded.

This study was the first time the current “gold standard” for evaluating influenza vaccines – a protective HAI titer of greater than 1:40 – has been evaluated in a well-controlled healthy volunteer challenge since the cutoff was established, and the first time NAI titer has been identified in a controlled trial to be an independent predictor of a reduction in all aspects of influenza. The authors declared no conflicts of interest.

Read the full study in mBio ( doi: 10.1128/mBio.00417-16 ).