Abstract
The influenza virus neuraminidase (NA) is primarily involved in the release of progeny viruses from infected cells—a critical role for virus replication. Compared to the immuno-dominant hemagglutinin, there are fewer NA subtypes, and NA experiences a slower rate of antigenic drift and reduced immune selection pressure. Furthermore, NA inhibiting antibodies prevent viral egress, thus preventing viral spread. Anti-NA immunity can lessen disease severity, reduce viral shedding, and decrease viral lung titers in humans and various animal models. As a result, there has been a concerted effort to investigate the possibilities of incorporating immunogenic forms of NA as a vaccine antigen in future vaccine formulations. In this review, we discuss NA-based immunity and describe several human NA-specific monoclonal antibodies (mAbs) that have a broad range of protection. We also review vaccine platforms that are investigating NA antigens in pre-clinical models and their potential use for next-generation influenza virus vaccines. The evidence presented here supports the inclusion of immunogenic NA in future influenza virus vaccines.
Highlights
Vaccination remains the most effective countermeasure against influenza virusassociated morbidity and mortality [1,2,3,4]
Of the N2 reactive monoclonal antibodies (mAbs), 86% reacted to the first pandemic H3N2 virus strain known to infect humans (A/Hong Kong/1/1968), 71% (10 of 14) of the antibodies reacted to the H2N2 influenza strain that circulated since 1957, eleven years prior, and 14% had cross-reactivity to heterosubtypic subtypes (N3 and N9)
We described the human antibody response to NA, the immuno-subdominant glycoprotein found on the surface of the influenza virion
Summary
Vaccination remains the most effective countermeasure against influenza virusassociated morbidity and mortality [1,2,3,4]. Current seasonal influenza vaccines target the immuno-dominant surface glycoprotein, the hemagglutinin (HA) (Figure 1A) [2,5,6], as HA is responsible for viral attachment to sialic acid receptors on the host cell and fusion of viral and host endosomal membranes [6,7]. Understanding the role of anti-NA antibodies in controlling influenza virus infection can be improved through the generation of monoclonal antibodies (mAbs). Even though there are several different vaccines against influenza virus, only a handful of the vaccines can induce an immune response against NA, and several of the licensed vaccines contain little to no (e.g., Flucelvax) antigenic NA [43]. Unlike antibody responses to natural infection, antibody responses to vaccination are short-lived, and antibody titers induced by vaccination may even decline within a given influenza season [44,54,55]. NA-specific human monoclonal antibodies (mAbs) that are induced by natural infection and vaccination will be further discussed in the upcoming sections
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