Mucosal delivery of a prefusogenic-F, glycoprotein, and matrix proteins-based virus-like particle respiratory syncytial virus vaccine induces protective immunity as evidenced by challenge studies in mice

Virology. 2024 Oct:598:110194. doi: 10.1016/j.virol.2024.110194. Epub 2024 Jul 31.

Abstract

RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.

Keywords: Delivery routes; Mucosal vaccine; Nasal; Pulmonary; Respiratory syncytial virus (RSV); Sublingual; Virus-like-particles (VLPs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Mucosal
  • Animals
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Female
  • Glycoproteins / administration & dosage
  • Glycoproteins / immunology
  • Immunity, Mucosal
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C*
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Syncytial Virus Infections* / prevention & control
  • Respiratory Syncytial Virus Vaccines* / administration & dosage
  • Respiratory Syncytial Virus Vaccines* / immunology
  • Respiratory Syncytial Virus, Human / immunology
  • Respiratory Syncytial Viruses / immunology
  • T-Lymphocytes / immunology
  • Vaccines, Virus-Like Particle* / administration & dosage
  • Vaccines, Virus-Like Particle* / immunology
  • Viral Fusion Proteins* / administration & dosage
  • Viral Fusion Proteins* / genetics
  • Viral Fusion Proteins* / immunology
  • Viral Matrix Proteins* / administration & dosage
  • Viral Matrix Proteins* / genetics
  • Viral Matrix Proteins* / immunology

Substances

  • Respiratory Syncytial Virus Vaccines
  • Antibodies, Viral
  • Vaccines, Virus-Like Particle
  • Viral Fusion Proteins
  • Viral Matrix Proteins
  • Immunoglobulin G
  • Glycoproteins
  • F protein, human respiratory syncytial virus