Lipid nanoparticle-delivered mRNA vaccine encoding the MOMP of <i>Chlamydia psittaci</i> elicits protective immune responses in BALB/c mice

<i>Chlamydia psittaci</i> is an important pathogenic zoonotic pathogen that infects birds and can be transmitted to humans and other animals. This research focused on creating an mRNA vaccine targeting <i>C. psittaci</i> and assessing its immunogenic and protective effects in BALB/c mice. We carried out a trial to prepare and assess an mRNA vaccine targeting <i>C. psittaci</i>. This study involves an mRNA vaccine encoding the major outer membrane protein (MOMP), produced via an <i>in vitro</i> transcription system and encapsulated in lipid nanoparticles (LNPs). The mRNA vaccine was constructed by synthesizing non-replicating mRNA encoding MOMP. LNPs were produced and characterized for their particle morphology, size, and cytotoxicity. Histopathological analysis and indirect immunofluorescence assay of lung tissue demonstrated that mRNA vaccines effectively reduce chlamydial infection and shedding in BALB/c mice. The western blot assay confirmed the successful expression of the recombinant MOMP mediated by the target mRNA in HeLa cells. Immunization with the LNP-Opt-mRNA vaccine induced a strong immune response in mice. Mice immunized with the LNP-Opt-mRNA vaccine exhibited lower levels of <i>C. psittaci</i> load and decreased concentrations of interferon-γ, TNF-α, and IL-6 in the lungs compared to the PBS group. The study successfully constructed and developed the LNP-mRNA vaccine expressing the MOMP of <i>C. psittaci</i>. The vaccine demonstrated strong immunogenicity, inducing effective humoral and cellular immune responses that significantly decreased pulmonary <i>C. psittaci</i> burden in mice. These findings provide a basis for designing mRNA vaccines against <i>C. psittaci</i> and similar respiratory pathogens.IMPORTANCE<i>Chlamydia psittaci</i> is a significant threat to public health due to its zoonotic nature and capability to spread from birds to humans and other animals. It is necessary to develop an effective preventive measure. This study introduces an innovative strategy against <i>C. psittaci</i> using an mRNA vaccine that encodes the major outer membrane protein, demonstrating potential in eliciting robust immune responses in mice. The work emphasizes the efficacy of mRNA vaccines in inducing humoral and cellular immune responses, significantly decreasing the lung <i>C. psittaci</i> burden in mice and underscoring their potential against respiratory pathogens. The study indicates that lipid nanoparticle-mRNA vaccines may be a useful technique for treating and preventing <i>C. psittaci</i> infections, providing valuable insights for developing vaccines against other <i>Chlamydia</i> species and respiratory pathogens. Finally, this study provides a theoretical foundation and practical experience for the production of <i>C. psittaci</i> vaccines, paving the way for further exploration of mRNA vaccine platforms and co-delivery strategies to enhance immune responses.