Baculovirus vectors expressing F proteins in combination with virus-induced signaling adaptor (VISA) molecules confer protection against respiratory syncytial virus infection.

Abstract

Baculovirus has been exploited for use as a novel vaccine vector. To investigate the feasibility and efficacy of recombinant baculoviruses (rBVs) expressing respiratory syncytial virus (RSV) fusion (F) proteins, four constructs (Bac-tF/64, Bac-CF, Bac-CF/tF64 and Bac-CF/tF64-VISA) were generated. Bac-tF64 displays the F ectodomain (tF) on the envelope of rBVs, whereas Bac-CF expresses full-length F protein in transduced mammalian cells. Bac-CF/tF64 not only displays tF on the envelope but also expresses F in cells. Bac-CF/tF64-VISA comprises Bac-CF/tF64 harboring the virus-induced signaling adaptor (VISA) gene. After administration to BALB/c mice, all four vectors elicited RSV neutralizing antibody (Ab), systemic Ab (IgG, IgG1, and IgG2a), and cytokine responses. Compared with Bac-tF64, mice inoculated with Bac-CF and Bac-CF/tF64 exhibited an increased mixed Th1/Th2 cytokine response, increased ratios of IgG2a/IgG1 antibody responses, and reduced immunopathology upon RSV challenge. Intriguingly, co-expression of VISA reduced Th2 cytokine (IL-4, IL-5, and IL-10) production induced by Bac-CF/tF64, thus relieving lung pathology upon a subsequent RSV challenge. Our results indicated that the Bac-CF/tF64 vector incorporated with the VISA molecule may provide an effective vaccine strategy for protection against RSV.

• Authors: Yuan Zhang, Lei Qiao, Xiao Hu, Kang Zhao, Yanwen Zhang, Feng Chai, Zishu Pan
• Journal: Vaccine (Vaccine) Vol. 34 Issue 2 Pg. 252-260 (Jan 04 2016) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 26643933 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Antibodies, Neutralizing
• Antibodies, Viral
• Cytokines
• F protein, human respiratory syncytial virus
• Immunoglobulin G
• Respiratory Syncytial Virus Vaccines
• Vaccines, Synthetic
• Viral Fusion Proteins

Topics

• Adaptor Proteins, Signal Transducing (genetics, immunology)
• Animals
• Antibodies, Neutralizing (blood)
• Antibodies, Viral (blood)
• Baculoviridae (genetics)
• Cytokines (metabolism)
• Female
• Genetic Vectors
• Immunoglobulin G (blood)
• Mice, Inbred BALB C
• Respiratory Syncytial Virus Infections (prevention & control)
• Respiratory Syncytial Virus Vaccines (administration & dosage, genetics, immunology)
• Sf9 Cells
• Vaccines, Synthetic (administration & dosage, genetics, immunology)
• Viral Fusion Proteins (genetics, immunology)