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.