The Cooperation of IL-29 and PLGA Nanoparticles Improves the Protective Immunity of the gD-1 DNA Vaccine Against Herpes Simplex Virus Type 1 in Mice

Abstract

ABSTRACT In clinical practice, the low immunogenicity and low stability of the DNA plasmid vaccine candidates are two significant shortcomings in their application against infectious diseases. To overcome these two disadvantages, the plasmid expressing IL-29 (pIL-29) as a genetic adjuvant and polylactic-co-glycolic acid (PLGA) as a non-viral delivery system were used, respectively. In this study, the pIL-29 encapsulated in PLGA nanoparticles (nanoIL-29) and the pgD1 encapsulated in PLGA nanoparticles (nanoVac) were simultaneously applied to boost immunologic responses against HSV-1. We generated spherical nanoparticles with encapsulation efficiency of 75 ± 5% and sustained the release of plasmids from them. Then, Balb/c mice were subcutaneously immunized twice with nanoVac+nanoIL-29, Vac+IL-29, nanoVac, Vac, nanoIL-29, and/or IL-29 in addition to negative and positive control groups. Cellular immunity was evaluated via lymphocyte proliferation assay, cytotoxicity test, and IFN-γ, IL-4, and IL-2 measurements. Mice were also challenged with 50X LD50 of HSV-1. The nanoVac+nanoIL-29 candidate vaccine efficiently enhances CTL and Th1-immune responses and increases the survival rates by 100% in mice vaccinated by co-administration of nanoVac and nanoIL-29 against the HSV-1 challenge. The newly proposed vaccine is worth studying in further clinical trials, because it could effectively improve cellular immune responses and protected mice against HSV-1.