Transdermal delivery of plasmid encoding truncated nucleocapsid protein enhanced PRRSV-specific immune responses

Abstract

Background: Porcine Reproductive and Respiratory Syndrome virus (PRRSV) induces several immunomodulatory mechanisms that resulted in delayed and ineffective anti-viral immune responses. Recently, it has been shown that intradermal immunization of plasmid encoding truncated nucleocapsid protein (pORF7t) could reduce PRRSV-induced immunomodulatory activities and enhances anti-PRRSV immunity in vaccinated pigs. However, intradermal immunization may not be practical for farm setting. Currently, there are several transdermal delivery systems available in the market, although they were not originally designed for plasmid delivery.

Objectives: To investigate the potential use of a transdermal delivery system for delivering of pORF7t and its immunological outcomes.

Method: The immunomodulatory effects induced by transdermal delivery of pORF7t were compared with intradermal immunization in an experimental pig model. In addition, immunomodulatory effects of the DNA vaccine were determined in the fattening pigs kept in a PRRSV-positive farm environment, and in the experimental pigs receiving heterologous prime-boost, pORF7t-modified live vaccine (MLV) immunization.

Result: The patterns of PRRSV-specific cellular responses induced by transdermal and intradermal immunizations of pORF7t were similar. Interestingly, the pigs transdermally immunized with pORF7t exhibited higher number of PRRSV-specific CD8(+)IFN-γ(+) cells. Pigs immunized with pORF7t and kept at PRRSV-positive environment exhibited enhanced PRRSV-specific IFN-γ(+) production, reduced numbers of regulatory T lymphocytes (Tregs) and lower lung scores at the end of the finishing period. In the heterologous prime-boost experiment, priming with pORF7t prior to MLV vaccination resulted in significantly higher numbers of CD3(+)IFN-γ(+) subpopulations, lower numbers of PRRSV-specific CD3(+)IL-10(+) cells and Tregs, and rapid antibody responses in immunized pigs.

Conclusion: Transdermal immunization with pORF7t reduced PRRRSV-induced immunomodulatory effects and enhanced long-term PRRSV-specific cellular responses in vaccinated pigs. Furthermore, heterologous DNA-MLV prime-boost immunization significantly improved the quality of PRRSV-specific cellular and humoral immunity. The information could benefit the future development of PRRSV management and control strategies.

Keywords: DNA vaccine; Needle-free injection; Nucleocapsid protein; PRRSV; Transdermal; Tregs.