Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Stephen R. Welch, Jessica R. Spengler, Sarah C. Genzer, JoAnn D. Coleman-McCray, Jessica R. Harmon, Teresa E. Sorvillo, Florine E. M. Scholte, Sergio E. Rodriguez, Justin T. O’Neal, Jana M. Ritter, G Ficarra, Katherine Davies, Markus H. Kainulainen, Elif Karaaslan, Éric Bergeron, Cynthia S. Goldsmith, Michael K. Lo, Stuart T. Nichol, Joel M. Montgomery, Christina F. Spiropoulou
Abstract
Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease.