Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals, which spreads rapidly . The disease affects many areas of the world, often causing extensive epizootics in livestock, particularly farmed cattle and swine, although sheep, goats and many wild species are also susceptible [1–2]. High morbidity, a complex host-range and broad genetic diversity make FMD prevention and control exceptionally challenging . In most countries, susceptible livestock are immunized with inactivated foot-and-mouth disease virus (FMDV) vaccine in order to control the disease. Finding truly safe and effective vaccines, especially those that induce cell-mediated immunity, is the key to prevent and control the disease.
Adjuvant development plays a major role in vaccine technology . The reasonable use of adjuvants in vaccines not only lessens the use of antigens, but also stimulates the immune system quickly and enhances the immune response. The choice of adjuvant is particularly important. Several kinds of vaccine adjuvants have been studied for their potency to promote immune responses to FMDV vaccines. These adjuvants include mineral oil (ISA-206 and ISA-201) [4–6], saponins (Quil-A) , Toll-like receptor (TLR) ligands (targeting pattern recognition receptors) [8–11], cytokines (IFN-a, IFN-g, IL-1, IL-2, IL-15, IL-18 and GM-CSF) [12–14], liposomes . Current the commercial FMDV adjuvants used include ISA-206 and aluminum. Oil emulsions mainly rely on the strong reactogenicity to induce immunoreactions, which normally trigger severe side effects including hemolysis , swelling or necrosis at the injection site . Aluminum hydroxide phosphate (Alum) is approved by the FDA for use in humans because of its safety and efficacy . Nevertheless, Alum typically induces a classical antibody-mediated (Th2) response rather than cell-mediated (Th1) immunity, and therefore is not suitable for vaccination against diseases such as intracellular infections .The FDA-approved adjuvant also has undesirable features, it is non-biodegradable and consequently remains in situ longer than one year . Alum also frequently produces a strong inflammatory reaction at the injection site . Although some new adjuvants have been developed in recent years, but excellent adjuvant with good safety, efficacy, targeting, stability, controllable release, highly efficient immunity and low cost may be a hot research direction in the future.
Nanoparticles (NPs) and nanomaterials show great potential as next-generation adjuvants with desirable physicochemical features and reduced undesirable drawbacks and side effects . To date, NPs such as mesoporous silica NPs , chitosan NPs , gold NPs , poly (D,L-lactic-co-glycolic acid) (PLGA) NPs , clay nanomaterials (i.e. layered double hydroxide and hectorite) [27–28] have proven their capacity to boost immune responses as effective adjuvants.
Layered double hydroxide (LDH) is hydrotalcite-like clay, represented by the chemical formula [M2 + 1−xM3 + x(OH)2]X++[An−]x/n·mH2O . LDHs are formed by weathering of basalt in the nature . LDH is a layered structure: the laminates have a structural positive charge, and the interlayers are composed of anions and water molecules. The interlayers are bound together by electrostatic interaction. Recent results have demonstrated that dispersion-stable LDH NPs are efficient vaccine carriers, stimulate higher levels of antibodies for a longer period, maturate dendritic cells (DCs) and promote stronger specific T cell immune responses . For example, antigen BSA-Cy7 loaded LDH complexes generate loosely structured agglomerates either in solution or within nodules formed at the injection site and recruit immune cells into injection nodules and over a prolonged period . LDH-adjuvanted multiple-antigen vaccine formulations can efficiently stimulate strong humoral, cellular and mucosal immune responses that are capable of preventing E. coli from adhering to mammalian cells more efficiently than the commercial adjuvant formulation [27, 33]. A dispersion-stable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth . Therefore, LDH is a promising adjuvant vaccine due to the small particle size, stable dispersion, large specific surface area, positive charge, large cargo load, sustained release, easy absorption, low toxicity, low cost, and significantly improved the cellular immune response.
FMD vaccines not only focus on antigens but also focus on the adjuvant technology. Efficacy, source, cost and safety should be taken into account in adjuvant selection. In this study, LDH NPs were prepared by hydrothermal synthesis, and their properties analyzed. The mouse is a typical model animal and one of the representatives of typical mammals. The immune effects in mice were initially easy to observe. Pigs are susceptible to foot-and-mouth disease. It is practical to evaluate the effects of vaccines and adjuvants. The effects of LDH as adjuvant on inactivated FMDV vaccines were further evaluated compared with the commercial ISA-206 adjuvant in mice and pigs. LDH may be an effective and safe adjuvant improve FMD vaccine efficacy.