Reversible Mannosylation as a Covalent Binding Adjuvant Enhances Immune Responses for Porcine Circovirus Type 2 Vaccine

Abstract

Capsid protein of porcine circovirus type 2 (PCV2) is an ideal subunit vaccine candidate for the postweaning multisystemic wasting syndrome. In this study, mannan-mediated targeting of PCV2ΔCap42‑233 protein to antigen presenting cells (APCs) was investigated for the development of PCV2 vaccine. Mannan was attached to PCV2ΔCap42‑233 protein via an acid sensitive Schiff base reaction. The mannosylated protein was endowed with the capacity to target the mannose receptor on APCs as well as the ability of controlled release of the antigen in the acidic condition of the lysosome. Finally, the immune response of mannosylated PCV2ΔCap42‑233 protein in mice was evaluated. The mannosylated protein exhibited the ability to stimulate humoral immune response and enhance the immunity. Thus, acid-sensitive and APCs-targeting mannosylated PCV2ΔCap42‑233 protein represents a promising candidate for the potential commercial application as an efficient vaccine against porcine circovirus.

Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action

“…Mannan also activates the inflammasome, leading to caspase 1 and NF-κB activation, with production of IL-1β, IL-6 and TNF 264 . Mannan structures either in native, oxidized or reduced form have been conjugated to protein-based antigens and carriers as antigen-presenting cell-targeting adjuvant systems, resulting in enhanced antigen uptake and presentation, and increased T H 1/T H 2 responses 265 – 269 . Notably, clinical trials with oxidized mannan–MUC1 vaccine demonstrated its safety and immunogenicity, showing antibody and cellular clinical responses that protected patients with early-stage breast cancer from recurrence 270 – 272 .…”

Recent advances in antigen targeting to antigen-presenting cells in veterinary medicine

“…Mice immunized intradermally with mannosylated PCV2 nanoparticles presented higher levels of IgG, IL-4, and IL-2 than the nontargeted group, even in the absence of other adjuvants. Additionally, the study showed that the mannosylated protein presented a slow release when exposed to low pH in vitro, simulating lysosome conditions and furthering the potential of using mannosylation as a controlled-release tool for drugs (85).…”

Carbohydrate Immune Adjuvants in Subunit Vaccines

“…It has been suggested that the oxidizing conditions allowed mannan aldehyde groups to form Schiff bases not only with antigens, but also with APCs, inducing strong antitumor immunity by targeting the antigen to the intracellular processing pathway for presentation with MHC I molecules. However, this was contradicted by another study that showed high antibody responses against vaccines bearing oxidized mannan [ 98 ]. A nanoparticle-based vaccine candidate (200–800 nm) against porcine circovirus type 2 (PCV2) containing oxidized mannan attached to PCV2 ΔCap42-233 protein via an acid-sensitive Schiff base reaction was developed.…”