Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages

Abstract

The mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4 + T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration.

Liposomes: a promising carrier for respiratory syncytial virus therapeutics

“…Subcutaneous (S.C.) administration of these lipid nanoparticles produce an innate immune response, but the reason for using low surface charged lipids seems unclear. However, use of liposomes can stabilize the RNA for long-term and can eliminate the risk of new infections caused by carrier-based vaccine [111,112]. This finding matches with the research by Lee and colleagues,…”

Respiratory Syncytial Virus (RSV) Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology

“…Correspondingly, the robust human cellderived cytokine response to RSV in HIS mice is likely responsible for the observed loss of body weight. In addition, the cytokines and chemokines recruit immune cells to the site of infection and induce pathology and mucus hyperplasia (41)(42)(43), as was observed in RSV-infected HIS mice. The inefficiency with which immunodeficient NSG mice cleared the RSV infection, a lack of weight loss, and the absence of significant changes in lung histopathology are consistent with the findings described in previous reports (44,45).…”

Nanoparticle Vaccines Against Infectious Diseases

“…Co-incubation of nano-TiO 2 and Fe 3 O 4 -TiO 2 with DCs resulted in an increased production of TNF-α, and also upregulated the expression of CD80, CD86 and MHC class II molecules through the NF-κB signaling pathway ( 163 ). In this way, immunization efficacy of various NP formulations such as erythrocyte membrane-enveloped poly(D,L-lactide-co-glycolide) (PLGA) NPs for antigenic peptide (hgp10025-33) and TLR-4 agonist, VLPs expressing RSV glycoproteins, chitosan-coated EphrinA1-PE38/GM-CSF, and several others have been improved ( 171 – 177 ). NPs can also control cell polarization and differentiation.…”