Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus

TLDR

Respiratory syncytial virus is a global health threat lacking a vaccine, and the prefusion F glycoprotein has emerged as the key neutralizing target, opening new vaccine design avenues. The study aimed to create a self‑assembling protein nanoparticle that displays a prefusion‑stabilized DS‑Cav1 F trimer in a repetitive array on its surface. Using a two‑component scaffold, the authors produced highly ordered, monodisperse immunogens that present DS‑Cav1 trimers at controllable densities. In mice and nonhuman primates, the full‑valency nanoparticle presenting 20 DS‑Cav1 trimers induced neutralizing antibody responses roughly ten times higher than trimeric DS‑Cav1, validating the platform and encouraging further development.

Abstract

Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.