Baculovirus vectors expressing F proteins in combination with virus-induced signaling adaptor (VISA) molecules confer protection against respiratory syncytial virus infection. Issue 2 (4th January 2016)

• Record Type: Journal Article
• Authors: Zhang, Yuan; Qiao, Lei; Hu, Xiao; Zhao, Kang; Zhang, Yanwen; Chai, Feng; Pan, Zishu
• Is Part Of: Vaccine. Volume 34:Issue 2(2016)
• Page Start: 252
• Page End: 260
• Publication Date: 2016-01-04
• Subjects: Baculovirus -- Respiratory syncytial virus -- F protein -- Vaccine -- VISA; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2015.11.027
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: We constructed recombinant baculoviruses (rBVs) expressing RSV F proteins. Bac-CF/tF64 induced mixed Th1/Th2 cytokine responses with reduced immunopathology. Co-expression of VISA reduced Th2 cytokines production induced by Bac-CF/tF64. Co-expression of VISA relieved pathology of vaccinated mice upon RSV challenge. 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.