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NAI titers better predict influenza protection
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New evidence indicates that high neuraminidase inhibition titers better predict protection against influenza and reduced disease severity than hemagglutinin inhibition titers traditionally used to measure immunity, according to researchers at the National Institute of Allergy and Infectious Diseases.
As a result, Matthew J. Memoli, MD, MS, director of the Clinical Studies Unit in the Laboratory of Infectious Diseases at NIAID, and colleagues, suggested that antibody levels against neuraminidase (NA), an influenza surface protein that permits newly formed viruses to exit a host cell, be considered when assessing influenza susceptibility after vaccination, and as a “critical target” in future vaccine platforms.
Anthony S. Fauci
“Each year between 3,000 and 49,000 people in the United States die as the result of seasonal influenza and its complications,” Anthony S. Fauci, MD, NIAID director, said in a press release. “Annual vaccination against seasonal flu continues to be the most effective way to protect against infection, and this new study provides some interesting clues about how we might improve the level of protection that flu vaccines provide.”
Seasonal influenza vaccines are currently designed to induce high antibody levels against hemagglutinin — a protein that enables the influenza virus to enter and infect human cells, the release said. Data from recent influenza seasons, however, show that current vaccines are “greatly underperforming,” with vaccine effectiveness ranging from 10% to 56% (mean, 40%), according to Memoli and colleagues.
To investigate the lack of effectiveness, the researchers launched a well-controlled human challenge study with the influenza A 2009 (H1N1) pandemic virus to examine the role of hemagglutinin inhibition (HAI) titers as a correlate of protection.
Matthew J. Memoli
“The idea behind this study was to re-evaluate the bar that was previously established for evaluating a person’s immune response to influenza vaccines,” Memoli said in the press release. “We wanted to test the conventional wisdom and see if people with high levels of HA antibodies were less likely to develop mild-to-moderate influenza disease [(MMID)] compared with those with lower HA antibody levels.”
The researchers administered an intranasal dose of influenza A 2009 (H1N1) to 25 healthy volunteers with a high HAI titer at or above 1:40, and to 40 healthy volunteers with a lower level below 1:40. There were no significant differences in age, gender, race or ethnicity between the titer groups. The participants were observed daily during a 9-day inpatient quarantine and were further monitored for 2 months after discharge.
While participants with high HAI titers were significantly less likely to develop MMID compared with those with low HAI titers (24% vs. 72%; P < .001) and experienced a shorter duration of symptoms and viral shedding, there was no difference in the proportion of participants reporting influenza symptoms (80% vs. 88%).
“If these results are consistent with outcomes following natural influenza infection, the protection afforded by an HAI titer of ≥ 1:40 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,” Memoli and colleagues wrote. “This finding is important to consider for future studies and may account for some of the inconsistencies in current evaluations of influenza vaccine performance that do not take disease severity/duration into account, as many individuals receiving an efficacious vaccine might still report influenza symptoms following viral exposure/infection.”
In contrast, an analysis adjusted for NA inhibition (NAI) titers demonstrated that participants with higher baseline levels had fewer symptoms and severity in addition to shorter symptom and viral shedding durations. They also were significantly less likely to develop MMID vs. those with low NAI titers (44% vs. 100%; P < .001).
The researchers noted that, overall, participants with higher baseline levels of both HAI and NAI titers had reduced disease severity vs. those with low titers of both HAI and NAI, or HAI alone. There were no participants with high HAI titers and low NAI titers.
“Ultimately, both HAI and NAI titers together may be a better predictor of MMID and disease severity than either alone, but these data suggest that NAI titer is a stronger correlate of disease severity than is HAI titer alone,” Memoli and colleagues wrote. – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.
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