Antibody-based therapies against Andes virus: from neutralization to Fc-mediated protection

Abstract Andes virus, the principal etiological agent of hantavirus cardiopulmonary syndrome in South America, is a zoonotic pathogen associated with case fatality rates of up to 40%. Despite its high clinical burden and unique capacity for person-to-person transmission among hantaviruses, no licensed vaccines or specific antiviral therapies are currently available. These limitations underscore the need to develop effective therapeutic and prophylactic strategies against ANDV. Monoclonal antibodies have emerged as a promising platform for the prevention and treatment of viral diseases because of their high specificity, rapid development, and potential for optimization through antibody engineering. While virus neutralization remains a key mechanism of protection, Fc-mediated effector functions, including antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent complement deposition, have increasingly been recognized as critical contributors to antiviral immunity and therapeutic efficacy. Evidence from antibody-based interventions against other viral pathogens has demonstrated the clinical feasibility of this approach and provides a strong rationale for its application to ANDV. In this review, we summarize current advances in antibody-based therapies targeting ANDV, discuss the contribution of Fc-mediated effector functions to antiviral protection, and highlight emerging strategies to optimize antibody engineering for the development of more effective therapeutic and prophylactic interventions against this neglected pathogen.