Study Provides Clues for Improving Effectiveness of Flu Vaccine

A study conducted by scientists at the National Institute for Allergy and Infectious Diseases (NIAID) has found that seasonal flu vaccines work better if they stimulate an immune response to the flu surface protein neuraminidase (NA), which enables newly formed flu viruses to exit the host cell and cause further viral replication in the body. Currently, seasonal flu vaccines are designed to induce high levels of protective antibodies against hemagglutinin (HA), which enables the virus to enter a human cell and initiate infection. Traditionally, HA antibodies levels have been used to guide vaccine strain selection and to infer how effective that vaccine might be against circulating viruses until field studies are available.

In the human challenge study (in which individuals are exposed to disease-causing pathogens under carefully controlled conditions), NIAID researchers enrolled 65 healthy volunteers aged 18 years to 50 years and measured the levels of existing anti-HA and anti-NA antibodies in participants’ blood. Based on those results, participants were placed in two groups: those with high levels of anti-HA antibodies (25 participants) and those with low levels of anti-HA antibodies (40 participants). Each of the volunteers was then administered an intranasal dose (1 mL) of 2009 H1N1 influenza virus, after which they were required to stay in the study unit for nine days where they were monitored by medical staff 24 hours daily. After the nine-day testing period, participants were discharged after completing two days of negative flu tests. After that, they had four follow-up visits over an eight-week period.

The researchers found that those with high levels of anti-HA antibodies experienced significantly lower incidence of mild-to-moderate influenza disease and some reduction in its duration compared with participants with low HA antibody levels. However, they also found that participants were just as likely to experience some flu symptoms as those with low levels of HA antibodies. Those results suggest that while high HA antibody levels may limit viral shedding and, thus, spread the virus from person to person, these levels may not prevent the development of flu symptoms, which may explain why some people who receive the flu vaccine might still get the flu. What surprised the researchers was that participants with high levels of NA antibodies experienced less severe disease, a shorter duration of viral shedding and symptoms, and fewer and less severe symptoms compared with those with high HA antibody levels.

The researchers concluded that HA and NA antibody levels together may be a better predictor of whether someone develops mild-to-moderate influenza disease and severity of symptoms than either factor alone; however, NA antibodies are the stronger factor for determining disease severity. And, they suggest that the role of NA immunity should be considered when studying influenza susceptibility, and NA antigens should be considered in the design of future flu vaccine platforms.