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PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

ABSTRACT: Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was superior to the Sm mRNA-LNP vaccine at inducing antibody and cellular immune responses in mice. Evaluation of the immunogenicity and efficacy of the S mRNA vaccine in piglets confirmed that it induced robust PEDV-specific humoral and cellular immune responses in vivo. Importantly, the S mRNA-LNP vaccine not only protected actively immunized piglets against PEDV but also equipped neonatal piglets with effective passive anti-PEDV immunity in the form of colostrum-derived antibodies after the immunization of sows. Our findings suggest that the PEDV-S mRNA-LNP vaccine is a promising candidate for combating PEDV infection.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) continues to harm the global swine industry. It is important to develop a highly effective vaccine to control PEDV infection. Here, we report a PEDV spike (S) mRNA vaccine that primes a potent antibody response and antigen-specific T-cell responses in immunized piglets. Active and passive immunization can protect piglets against PED following the virus challenge. This study highlights the efficiency of the PEDV-S mRNA vaccine and represents a viable approach for developing an efficient PEDV vaccine.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC10865985 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

Zhao Yongxiang Y Fan Baochao B Song Xu X Gao Jie J Guo Rongli R Yi Cheng C He Zhaoming Z Hu Hongpeng H Jiang Jianhao J Zhao Lixiang L Zhong Tianyi T Li Bin B

mBio 20240117 2

Porcine epidemic diarrhea virus (PEDV), a swine enteropathogenic coronavirus, causes severe diarrhea in neonatal piglets, which is associated with a high mortality rate. Thus, developing effective and safe vaccines remains a top priority for controlling PEDV infection. Here, we designed two lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) vaccines encoding either the full-length PEDV spike (S) protein or a multiepitope chimeric spike (Sm) protein. We found that the S mRNA-LNP vaccine was su ...[more]

PMID: 38231557

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Project description:Background/objectivesChlamydia (C.) psittaci is an avian respiratory pathogen that regularly infects budgerigars (Melopsittacus undulatus) and is a known zoonosis. This study aimed to evaluate the efficacy of a nucleoside-modified mRNA vaccine formulated in lipid nanoparticles (LNPs), either with (mRNA Galsomes) or without (mRNA LNPs) the glycolipid antigen α-Galactosylceramide, in protecting budgerigars against C. psittaci genotype A infection.MethodsThree groups of eight budgerigars received two intramuscular vaccinations with PBS, mRNA LNPs or mRNA Galsomes, and were subsequently challenged via aerosol with the C. psittaci genotype A strain 90/1051. Vaccine efficacy was assessed over 14 days post challenge by monitoring clinical signs, macroscopic and microscopic lesions, pathogen excretion and chlamydial burden in organs. Antibody levels were evaluated at baseline, after vaccination and post challenge.ResultsBoth mRNA LNPs and mRNA Galsomes induced significant serum antibody responses post booster. Vaccination significantly reduced clinical signs, chlamydial burden in the lungs and macroscopic lesions in conjunctiva, conchae, lungs and thoracic airsacs, compared to controls. Additionally, mRNA Galsomes-treated birds showed a significantly reduced lung inflammation and fewer macroscopic lesions in abdominal airsacs and liver, compared to non-vaccinated animals. These animals also experienced a significantly lower chlamydial burden in the spleen, fewer clinical signs at day 11 and fewer fecal shedding at day 14 post challenge, compared to mRNA LNP-treated animals.ConclusionsThis study demonstrated that mRNA vaccination confers partial protection against C. psittaci in budgerigars, with mRNA Galsomes appearing to provide enhanced efficacy. However, the absence of species-specific reagents for assessing cellular immunity in Psittaciformes limits a comprehensive understanding of vaccine-induced protection. The development of psittacine-specific T cell markers and cytokine assays is necessary to further elucidate immune mechanisms and optimize vaccine formulations.

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PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

Publications

PEDV-spike-protein-expressing mRNA vaccine protects piglets against PEDV challenge.

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