Virus-like nanoparticle and DNA vaccination confers protection against respiratory syncytial virus by modulating innate and adaptive immune cells

Respiratory syncytial virus (RSV) is an important human pathogen. Expression of virus structural proteins produces self-assembled virus-like nanoparticles (VLP). We investigated immune phenotypes after RSV challenge of immunized mice with VLP containing RSV F and G glycoproteins mixed with F-DNA (FdFG VLP). In contrast to formalin-inactivated RSV (FI-RSV) causing vaccination-associated eosinophilia, FdFG VLP immunization induced low bronchoalveolar cellularity, higher ratios of CD11c+ versus CD11b+ phenotypic cells and CD8+ T versus CD4+ T cells secreting interferon (IFN)-γ, T helper type-1 immune responses, and no sign of eosinophilia upon RSV challenge. Furthermore, RSV neutralizing activity, lung viral clearance, and histology results suggest that FdFG VLP can be comparable to live RSV in conferring protection against RSV and in preventing RSV disease. This study provides evidence that a combination of recombinant RSV VLP and plasmid DNA may have a potential anti-RSV prophylactic vaccine inducing balanced innate and adaptive immune responses.From the Clinical EditorThis study demonstrates that a combination of recombinant RSV virus-like nanoparticles and plasmid DNA may be utilized as a prophylactic vaccine against RSV, inducing balanced innate and adaptive immune responses.

Immunization of mice with a mixed vaccine (FdFG VLP) of virus-like nanoparticles (VLPs) containing respiratory syncytial virus (RSV) F and G glycoproteins and plasmid DNA encoding RSV F induced IgG2a antibodies dominantly specific for RSV F. After RSV challenge, FdFG VLP immunized mice controlled lung viral loads as well as showed higher levels of CD8+ T cells producing interferon-gamma and did not cause eosinophilia and pulmonary inflammatory disease compared to formalin-inactivated RSV immunized mice.Figure optionsDownload high-quality image (100 K)Download as PowerPoint slide