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Cellular immune correlates conferring protection against respiratory syncytial virus (RSV) but preventing vaccine-enhanced respiratory disease largely remain unclear. We investigated cellular immune correlates that contribute to preventing disease against human respiratory syncytial virus (RSV) by nanoparticle vaccine delivery. Formalin-inactivated RSV (FI-RSV) vaccines and virus-like nanoparticles carrying RSV fusion proteins (F VLP) were investigated in mice. The FI-RSV vaccination caused severe weight loss and histopathology by inducing interleukin (IL)-4 + , interferon (IFN)- γ  + , IL-4 + IFN- γ  + CD4 + T cells, eosinophils, and lung plasmacytoid dendritic cells (DCs), CD103 + DCs, and CD11b + DCs. In contrast, the F VLP-immune mice induced protection against RSV without disease by inducing natural killer cells, activated IFN- γ  + , and IFN- γ  + tumor necrosis factor (TNF)- α  + CD8 + T cells in the lung and bronchiolar airways during RSV infection but not disease-inducing DCs and effector T cells. Clodronate-mediated depletion studies provided evidence that alveolar macrophages that were present at high levels in the F VLP-immune mice play a role in modulating protective cellular immune phenotypes. There was an intrinsic difference between the F VLP and FI-RSV treatments in stimulating proinflammatory cytokines. The F VLP nanoparticle vaccination induced distinct innate and adaptive cellular subsets that potentially prevented lung disease after RSV infection.

journal of biomedical nanotechnology

Cellular Immune Correlates Preventing Disease Against Respiratory Syncytial Virus by Vaccination with Virus-Like Nanoparticles Carrying Fusion Proteins