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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.

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigen-displaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigen-displaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.