A lipid nanoparticle-based mRNA vaccine elicits immunity against porcine circovirus type 2 in mice.

Porcine circovirus type 2 (PCV2), the primary etiological agent of porcine circovirus-associated diseases (PCVADs), continues to cause substantial economic losses worldwide. Although commercially available vaccines have been widely deployed, they often fail to induce sufficient cellular immunity, which necessitates the development of improved vaccination strategies. This study reports the design and evaluation of a messenger RNA (mRNA)-based vaccine candidate targeting PCV2. The vaccine encodes the full-length capsid (Cap) protein, the principal target for neutralizing antibodies. For enhanced delivery and immunogenicity, the mRNA was encapsulated in lipid nanoparticles (LNP). Expression of the PCV2 Cap protein was confirmed in HEK-293T cells following transfection with the mRNA-LNP construct. In a mouse model, this vaccine elicited high titers of PCV2-specific IgG and potent virus-neutralizing antibodies, compared to a recombinant Cap subunit vaccine. Furthermore, the vaccine induced a robust Th1-polarized cellular immune response, marked by significant proliferation of antigen-specific CD8⁺ T cells and CD4⁺ T cells, enhanced interferon-gamma (IFN-γ) production, and expansion of T follicular helper cells and germinal center B cells in lymph nodes. Co-administration with a CpG ODN adjuvant further enhanced immunogenicity without compromising the vaccine's favorable safety profile. Collectively, these results indicate that the PCV2 mRNA-LNP vaccine represents a promising vaccine candidate worthy of further development against PCV2.IMPORTANCEPorcine circovirus type 2 (PCV2) is a widespread virus that causes severe disease in pigs, leading to significant economic losses in the swine industry worldwide. Existing vaccines often fail to stimulate strong cellular immunity, which is essential for long-lasting protection. In this study, we developed a novel messenger RNA (mRNA)-based vaccine encapsulated in lipid nanoparticles that encodes the PCV2 capsid protein. Our vaccine not only triggers potent antibody responses but also activates key immune cells, enhancing both humoral and cellular immunity. This represents the first mRNA-lipid nanoparticle vaccine against PCV2 and demonstrates the potential of mRNA technology to overcome limitations of traditional veterinary vaccines, offering a promising new tool for disease control in animals.