Original ArticleVirus-like nanoparticle and DNA vaccination confers protection against respiratory syncytial virus by modulating innate and adaptive immune cells
Graphical abstract
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.
Section snippets
Preparation of RSV VLPs, RSV F encoding DNA, and FI-RSV
Nanoparticle VLP consisting of an influenza virus matrix (M1) protein core and RSV glycoproteins F (RSV F VLP) or G (RSV G VLP) on the surface were produced using the insect cell expression system and characterized as described.16 Briefly, SF9 insect cells were infected with recombinant baculoviruses expressing M1 and RSV F or RSV G proteins, and RSV VLP nanoparticles released into cell culture media were purified by ultracentrifugation.16 The plasmid DNA encoding RSV F protein (RSV F DNA) was
A combined VLP and DNA vaccine induces high IgG2a/IgG1 antibody ratios
Both F VLP and G VLP were shown to raise similar RSV neutralizing titers and control lung viral loads.16 In addition, antibody responses specific for RSV G central domains were demonstrated to contribute to conferring protection and ameliorating RSV disease.22 We found that FdFG VLP was more effective in inducing higher levels of IgG2a antibodies (Th1 type) whereas F DNA alone was not highly immunogenic (Supplementary Figure S1). Therefore, to further evaluate the protective immune responses
Discussion
Protective immune correlates are not well understood because there is no licensed RSV vaccine. In particular, cellular phenotypes contributing to protection and disease remain largely unknown after RSV vaccination. Results in this study provide evidence that FdFG VLP could confer protection against RSV by preventing pulmonary eosinophilia and modulating cellular phenotypes as well as cellularity of infiltrates and IFN-γ secreting cells in addition to inducing Th1 type antibodies and cytokines.
Acknowledgment
The authors thank T. Kang for editing the manuscript.
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Cited by (0)
Funding information: This work was supported by National Institutes of Health/NIAID grants AI105170 (S.M.K.), AI093772 (S.M.K.), 1R01AI087798 (MLM), 1U19AI095227 (MLM), and NRF 2014R12014R1A2A2AA01004899 (FSQ).
The histology core facility in the Center for Inflammation, Immunity, & Infection was supported by Georgia Research Alliance. The following reagent was obtained through the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: Respiratory Syncytial Virus A2 F soluble protein, NR-28908.
All authors declare no conflicts of interest.