Fc-Mediated Effector Functions of Anti-NS1 Antibodies in Dengue

Abstract

The non-structural protein 1 (NS1) of dengue virus (DENV) plays a multifaceted role in viral pathogenesis and immune modulation. Although vaccine strategies have traditionally focused on neutralizing antibodies against the envelope (E) protein, recent evidence highlights the protective potential of anti-NS1 antibodies—particularly those that mediate Fc-dependent effector functions. These functions include antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), which collectively bridge adaptive antibody responses with innate immune activation. However, the outcomes of anti-NS1 responses are context-dependent: certain antibody specificities confer protection, while others may contribute to immunopathology. In this review, I synthesize current evidence on the roles of anti-NS1 antibodies in modulating Fc receptor engagement, subclass-specific responses, glycosylation patterns, and their effector functions. Understanding these mechanisms is essential for guiding rational vaccine design and the development of antibody-based diagnostics and therapeutics. By integrating the findings from both innate and adaptive immunology, this review emphasizes the importance of NS1 as a multifunctional immune determinant in dengue virus infection. © 2025 by the author.