Abstract
Virus-like particles (VLPs) have emerged as promising vaccine candidates against foot-and-mouth disease (FMD). However, such vaccines provide a relatively low level of protection against FMD virus (FMDV) because of their poor immunogenicity. Therefore, it is necessary to design effective vaccine strategies that induce more potent immunogenicity. In order to investigate the means to improve FMD VLP vaccine (VLPFMDV) immunogenicity, we encapsulated VLPs (MPL/DDA-VLPFMDV) with cationic liposomes based on dimethyldioctadecylammonium bromide (DDA) and/or monophosphoryl lipid A (MPL, TLR4 agonist) as adjuvants. Unlike inactivated whole-cell vaccines, VLPFMDV were successfully encapsulated in this MPL/DDA system. We found that MPL/DDA-VLPFMDV could induce strong cell-mediated immune responses by inducing not only VLP-specific IFN-γ+CD4+ (Th1), IL-17A+CD4+ (Th17), and IFN-γ+CD8+ (activated CD8 response) T cells, but also the development of VLP-specific multifunctional CD4+ and CD8+ memory T cells co-expressing IFN-γ, TNF-α, and IL-2. In addition, the MPL/DDA-VLPFMDV vaccine markedly induced VLP-specific antibody titers; in particular, the vaccine induced greater Th1-predominant IgG responses than VLPFMDV only and DDA-VLPFMDV. These results are expected to provide important clues for the development of an effective VLPFMDV that can induce cellular and humoral immune responses, and address the limitations seen in current VLP vaccines for various diseases.
Highlights
Foot-and-mouth disease virus (FMDV) can cause highly contagious foot-and-mouth disease (FMD) in cloven-hoofed livestock, cattle, sheep, goats and pigs [1,2]
Formulation; VLPFMDV only; dimethyldioctadecylammonium bromide (DDA)/VLPFMDV: VLPFMDV formulated with DDA; MPL/DDA/VLPFMDV: We first performed a Dynamic Light Scattering (DLS) analysis on five types (DDA only; MPL/DDA: MPL and DDA formulation; VLPFMDV: VLPFMDV formulated with DDA and MPL) of formulated VLPFMDV vaccines to confirm the VLPFMDV only; DDA/VLPFMDV : VLPFMDV formulated with DDA; MPL/DDA/VLPFMDV : VLPFMDV : particle sizes and successful formulation
VLPFMDV formulated with DDA and MPL) of formulated VLPFMDV vaccines to confirm the particle of 44.6 nm
Summary
Foot-and-mouth disease virus (FMDV) can cause highly contagious foot-and-mouth disease (FMD) in cloven-hoofed livestock, cattle, sheep, goats and pigs [1,2] This virus belongs to a prototypical member of the Aphthovirus of the Picornaviridae family, and is classified into seven distinct serotypes (O, A, C, SAT 1 to 3, and Asia 1), as well as >65 subtypes [3,4]. Chemically inactivated FMDV vaccines have proven to be effective in controlling FMD in endemic areas, the disease still affects millions of animals and continues to cause economic problems worldwide [8,9] These commercial vaccines have several immunological limitations, such as absent or very low immune memory and cell-mediated immunity, and limited cross-reactive immunity against multiple serotypes [10,11,12]. There is currently a clear demand for a new generation or platform of FMD vaccines, such as recombinant subunit vaccines, DNA vaccines, adenovirus vector vaccines, and virus-like particles (VLPs) that can replace or improve current FMD vaccines [7,13,14]
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