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Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species.
Cell Rep. 2022 08 02; 40(5):111160.CR

Abstract

Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.

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Authors+Show Affiliations

Peng L
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA.
Fang Z
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA.
Renauer PA
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA; Molecular Cell Biology, Genetics and Development Program, Yale University, New Haven, CT 06516, USA.
McNamara A
Department of Immunobiology, Yale University, New Haven, CT 06510, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06510, USA.
Park JJ
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA; M.D.-Ph.D. Program, Yale University, West Haven, CT 06516, USA.
Lin Q
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA.
Zhou X
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA.
Dong MB
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA; Department of Immunobiology, Yale University, New Haven, CT 06510, USA; M.D.-Ph.D. Program, Yale University, West Haven, CT 06516, USA; Immunobiology Program, Yale University, New Haven, CT 06510, USA.
Zhu B
Computational Biology and Bioinformatics Program, Yale University, New Haven, CT 06510, USA.
Zhao H
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; Computational Biology and Bioinformatics Program, Yale University, New Haven, CT 06510, USA; Department of Biostatistics, Yale University School of Public Health, New Haven, CT 06510, USA; Yale Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT 06510, USA.
Wilen CB
Department of Immunobiology, Yale University, New Haven, CT 06510, USA; Department of Laboratory Medicine, Yale University, New Haven, CT 06510, USA.
Chen S
Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA; System Biology Institute, Yale University, West Haven, CT 06516, USA; Center for Cancer Systems Biology, Yale University, West Haven, CT 06516, USA; Molecular Cell Biology, Genetics and Development Program, Yale University, New Haven, CT 06516, USA; M.D.-Ph.D. Program, Yale University, West Haven, CT 06516, USA; Immunobiology Program, Yale University, New Haven, CT 06510, USA; Computational Biology and Bioinformatics Program, Yale University, New Haven, CT 06510, USA; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA; Yale Center for Biomedical Data Science, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: sidi.chen@yale.edu.

MeSH

AnimalsAntibodies, NeutralizingAntibodies, ViralCOVID-19COVID-19 VaccinesHumansLiposomesMiddle East Respiratory Syndrome CoronavirusNanoparticlesRNA, MessengerSARS-CoV-2Spike Glycoprotein, CoronavirusVaccinationVaccines, SyntheticViral VaccinesmRNA Vaccines

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

35921835

Citation

Peng, Lei, et al. "Multiplexed LNP-mRNA Vaccination Against Pathogenic Coronavirus Species." Cell Reports, vol. 40, no. 5, 2022, p. 111160.
Peng L, Fang Z, Renauer PA, et al. Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Rep. 2022;40(5):111160.
Peng, L., Fang, Z., Renauer, P. A., McNamara, A., Park, J. J., Lin, Q., Zhou, X., Dong, M. B., Zhu, B., Zhao, H., Wilen, C. B., & Chen, S. (2022). Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. Cell Reports, 40(5), 111160. https://doi.org/10.1016/j.celrep.2022.111160
Peng L, et al. Multiplexed LNP-mRNA Vaccination Against Pathogenic Coronavirus Species. Cell Rep. 2022 08 2;40(5):111160. PubMed PMID: 35921835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiplexed LNP-mRNA vaccination against pathogenic coronavirus species. AU - Peng,Lei, AU - Fang,Zhenhao, AU - Renauer,Paul A, AU - McNamara,Andrew, AU - Park,Jonathan J, AU - Lin,Qianqian, AU - Zhou,Xiaoyu, AU - Dong,Matthew B, AU - Zhu,Biqing, AU - Zhao,Hongyu, AU - Wilen,Craig B, AU - Chen,Sidi, Y1 - 2022/07/19/ PY - 2021/12/13/received PY - 2022/05/07/revised PY - 2022/07/13/accepted PY - 2022/8/4/pubmed PY - 2022/8/9/medline PY - 2022/8/3/entrez KW - CP: Immunology KW - MERS-CoV KW - SARS-CoV KW - SARS-CoV-2 KW - cross-reactivity KW - mRNA vaccine KW - multiplexed vaccination KW - multispecies coronavirus vaccine KW - sequential vaccination KW - single-cell profiling KW - systems immunology SP - 111160 EP - 111160 JF - Cell reports JO - Cell Rep VL - 40 IS - 5 N2 - Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. SN - 2211-1247 UR - https://www.unboundmedicine.com/medline/citation/35921835/Multiplexed_LNP_mRNA_vaccination_against_pathogenic_coronavirus_species_ DB - PRIME DP - Unbound Medicine ER -