Co-immunization with virus-like particle and DNA vaccines induces protection against respiratory syncytial virus infection and bronchiolitis

Abstract

This study demonstrates that immunization with non-replicating virus-like particle (FFG VLP) containing RSV F and G glycoproteins together with RSV F DNA induced T helper type 1 antibody responses to RSV F similar to live RSV infection. Upon RSV challenge 21 weeks after immunization, FFG VLP vaccination induced protection against RSV infection as shown by clearance of lung viral loads, and the absence of eosinophil infiltrates, and did not cause lung pathology. In contrast, formalin-inactivated RSV (FI-RSV) vaccination showed significant pulmonary eosinophilia, severe mucus production, and extensive histopathology resulting in a hallmark of pulmonary pathology. Substantial lung pathology was also observed in mice with RSV re-infections. High levels of systemic and local inflammatory cytokine-secreting cells were induced in mice with FI-RSV but not with FFG VLP immunization after RSV challenge. Therefore, the results provide evidence that recombinant RSV FFG VLP vaccine can confer long-term protection against RSV without causing lung pathology.

Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency

“…2) because of the codon optimization and incorporation of the enhancer sequences in the vector backbone. Previous studies generated similar results in an IFN-g ELISPOT assay 23,24,50 ; however, we also performed granzyme B ELISPOT and 51 Cr-release assays to selectively recognize the cytolytic activity of HRSV-specific CD8 C T cells. Although including the M2 82-90 epitope in immunization against HRSV induced robust CD8…”

Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats

“…19,20 Protection was reported without causing RSV disease by immunization of mice with mixed F VLP and G VLP (FG VLP) vaccines with DNA plasmids expressing F proteins as evidenced by clearing lung viral loads and preventing pulmonary inflammation. 21 However, the efficacy and safety of RSV F, G, or FCG VLP vaccine platforms have not been studied in cotton rats, which is the main focus in this study. We have investigated the immunogenicity, RSV disease assessment (weight loss, AHR), efficacy, cytokine patterns to indicate the type of immune response upon RSV infection, and vaccine-associated safety of F, G, and FG VLP vaccines in cotton rats.…”

“…This result of additive effects on preventing RSV disease in cotton rats by FG VLP is similarly observed in a mouse model. 21 FI-RSV immune or na€ ıve cotton rats exhibited RSV disease such as weight loss and AHR after RSV infection. Cotton rats with FI-RSV showed high levels of IL-4 and inflammatory TNF-a cytokines compared with FG VLP immune cotton rats.…”

“…Lung tissue sections were stained with hematoxylin and eosin (H&E), periodic acid-schiff stain (PAS), and hematoxylin and congo red (H&CR) to assess histopathological changes, mucin expression, and eosinophils infiltration respectively as described previously. 21,32 Numerical assessment of histopathology was performed on a scale of 0-3 by blinded observers with the severity scoring system. 21,33 The mucin expression was detected with PAS-positive area.…”

“…21,32 Numerical assessment of histopathology was performed on a scale of 0-3 by blinded observers with the severity scoring system. 21,33 The mucin expression was detected with PAS-positive area. The degrees of pulmonary eosinophilia were indicated by eosinophil numbers present per 400£ field using H&CR stain.…”