African swine fever (ASF) is a severe and highly contagious viral disease affecting domestic pigs, caused by the African swine fever virus (ASFV) [1]. It is characterized by acute hemorrhagic symptoms and can lead to mortality rates of up to 100 % [2]. The first reported case of ASF in China occurred in 2018, resulting in substantial economic losses [3,4]. Numerous types of potential vaccines have been developed for ASF, including inactivated vaccines, subunit vaccines, DNA vaccines, virus-vectored vaccines, live attenuated vaccines, and epitope-based vaccines [[5], [6], [7]]. However, the majority of efforts to develop a safe and effective vaccine against ASF have been unsuccessful. Inactivated vaccines often fail to elicit robust immune responses in the host. Vectored and subunit vaccines offer only partial protection against virulent virus infection [8]. While attenuated live viruses can provide better protection, they carry potential risks of spreading [9]. Thus, there is an urgent need to develop a new generation of ASF vaccines.

Over the past few years, mRNA vaccines have demonstrated remarkable potential to revolutionize life sciences and medical research owing to their minimal risk of insertional mutagenesis, safety, efficacy, rapid and scalable production, and cost-effectiveness [10]. The emergence of the SARS-CoV-19 outbreak led to the rapid development of mRNA vaccines [11]. At present, mRNA vaccines are being employed to combat new COVID variants, influenza, and the herpes simplex virus [[11], [12], [13]]. Effective delivery systems are crucial for ensuring the protective efficiency of mRNA, including facilitating entry into cells and evading degradation by endosomes [14]. Currently, lipid nanoparticle (LNP) technology stands as the most commonly utilized nano-based platform for mRNA delivery [15]. LNP also enhances the translation of mRNA into antigens for subsequent presentation by major histocompatibility complexes (MHC) [16]. However, effectively targeting dendritic Cells (DCs) while efficiently avoiding degradation within endosomal/lysosomal remains a challenge with LNP [17]. The mannose receptor (MR) is highly expressed on the surface of antigen-presenting cells (APCs), including DCs and macrophages [18]. Targeted delivery of antigens to the MR on DCs can enhance antigen uptake and presentation, thereby regulating APC differentiation and maturation [19]. For example, liposomes modified with mannose and carrying ovalbumin (OVA) antigens have shown promise as potential lymphocyte-targeted liposomal vaccines [20]. ASFV is an enveloped double-stranded DNA virus that encodes over 150 proteins. Among these, the p30 protein, encoded by the viral gene CP204L, is one of the most abundantly expressed viral proteins during early ASFV infection [21,22]. Interestingly, the p30 protein stimulates cytotoxic T lymphocyte (CTL) responses [23,24]. Immunization of pigs with the baculovirus-expressed p30 protein has been shown to modify the disease course and provide partial protection against challenges with the pathogenic European ASFV E75 strain [25]. Furthermore, antibodies against the p30 protein have been demonstrated to inhibit viral internalization [26]. In this study, we have developed an mRNA vaccine candidate encoding the p30 protein. To enhance mRNA delivery efficiency, we optimized the LNP formulation by modifying mannose to obtain mRNA/Man-LNP. We then assessed the impact of mRNA/Man-LNP on both DC targeting and translation efficiency. Subsequently, we evaluated the immunogenicity and biosafety of mRNA/Man-LNP in mice. Additionally, we discussed the potential immunological applications of mRNA/Man-LNP and the limitations of this study.