W169 - Humanized Monoclonal Antibody Targeting the Nucleoprotein of Human Respiratory Syncytial Virus Elicits Protective Cellular Immunity in a Murine Infection Model

Catalina Andrade – Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile; Jorge Soto – Millennium Institute on Immunology and Immunotherapy, Universidad Andrés Bello; Jose Muñoz – Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile; Susan Bueno – Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile; Alexis Kalergis – Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile

Abstract Text: The human Respiratory Syncytial Virus (hRSV) is the main respiratory virus that causes infant hospitalization, leading to acute lower respiratory tract infections. The absence of approved vaccines for infants against hRSV highlights the need to explore innovative therapeutic formulations. This becomes particularly relevant in enhancing the efficacy of licensed prophylactic agents such as the monoclonal antibody (mAb) Palivizumab. Like Palivizumab, the recently approved mAb, Nirsevimab, exhibits neutralizing capabilities against the fusion protein of hRSV. Our laboratory has identified the nucleoprotein (N-hRSV), expressed on the surface of hRSV-infected cells, as an interesting target. Our team has successfully developed a humanized mAb anti-N-hRSV, and its impact in protecting against hRSV infection has undergone a comprehensive study. Using a BALB/c murine infection model, we observed that treating humanized mAb anti-N-hRSV significantly reduces the pathology associated with hRSV infection. The reduction in viral load and neutrophil infiltration in lung tissue evidenced this. Additionally, we performed co-culture assays of dendritic cells with purified T cells from the spleens of immunized mice. By flow cytometry we detected the activation of CD4+ T cells which has been evidenced by an increase in CD25 and CD69 markers. Moreover, ELISA assays showed an increase in IL-2 secretion in the mice immunized with anti-N-hRSV and infected, compared with the mice not treated with anti-N-hRSV antibody. Notably, we observed the promotion of effector and central T cell immunological memory. Accordingly, our results suggest a promising preclinical profile for the humanized mAb anti-N-hRSV as a potent candidate against this pathogen.