News about development of effective influenza vaccines always grabs the headlines due to the sheer number of patients potentially impacted by the disease. Recently, scientists from the National Institutes of Health (NIH) discovered that antiflu antibodies inhibit two different viral proteins, not just the intended target.
Hemagglutinin and neuraminidase are proteins present on the surface of the influenza virus. The former mediates virion attachment and fusion with host cell membranes, while the latter releases budding progeny virions from the cell surface that remain attached via hemagglutinin binding.
The study, published the Journal of Experimental Medicine, reveals that antibodies that recognize the viral surface protein hemagglutinin can also inhibit neuraminidase. This, the scientists say, enhances antibody neutralization of the virus and activates innate immune cells with antiviral activity.
Current flu vaccines induce antibodies that recognize the hemagglutinin head and inhibit its ability to mediate viral entry, but the hemagglutinin head mutates rapidly, resulting in vaccine-resistant influenza strains. In contrast, the hemagglutinin stem domain is significantly more resistant to mutations, suggesting a better target for universal flu vaccines.
The NIH researchers report that the ability of antistem antibodies to inhibit neuraminidase enabled animals to better survive severe influenza infections. They believe this may be largely due to the role that neuraminidase normally plays in stopping the activation of innate immune cells with antiviral activity. To buttress this concept, the researchers found that the FDA-approved neuraminidase inhibitor oseltamivir further boosted the ability of antistem antibodies to activate immune cells exposed to influenza virus.
“The ability of neuraminidase inhibitors to enhance ... immune cell activation [by anti-stem antibodies] bound to viruses or infected cells suggests the possible clinical synergy between neuraminidase inhibitors and [anti-stem antibodies] in humans,” the authors write. In addition, this new understanding of how antistem antibodies exert their protective effects strengthens the design of universal flu vaccines targeting the hemagglutinin stem.In other flu vaccine–related news, this issue’s article, “The Impact of Statin Therapy on Influenza-Vaccine Response” (page 16) by Hailey Button, PharmD Candidate 2020; Alexander Ferrara, PharmD; and Gabriela Cipriano, PharmD, reports that patients who take statins may have a reduced immune response to the influenza vaccine compared with patients who do not take statin medications. Nevertheless, the authors say that data are insufficient to support withholding influenza vaccine in a patient receiving statin therapy. They also point out that information is lacking to support withholding statin therapy from patients in whom the seasonal influenza immunization is indicated. The authors conclude that the benefit of statin therapy for preventing cardiovascular disease outweighs the risk of a reduced influenza-vaccine response, and the benefit of vaccination outweighs the risk of a reduced response in patients receiving statin therapy.