Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
Open accessAbstract
Summary: An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority 1 . Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited T H 1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with T H 2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Preclinical trials showed MRT5500 induced a Th1-biased immune response in mice and non-human primates and prevented Th2-bias response which can induce vaccine-related enhanced respiratory disease (VAERD).
“Results of preclinical trials showed that MRT5500 induced a Th1-biased immune response in mice and non-human primates and prevented Th2-bias response which can induce vaccine-related enhanced respiratory disease (VAERD).433–435”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [435]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286 · see citing works
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020) · Science · doi:10.1126/science.abb2507 · Cited by 8,897 · see citing works
Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein
Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020) · doi:10.1101/2020.02.19.956581 · Cited by 8,586 · see citing works
Structural basis of receptor recognition by SARS-CoV-2
Shang, J., Ye, G., Shi, K., Wan, Y., Luo, C., Aihara, H., Geng, Q., Auerbach, A., & Li, F. (2020) · Nature · doi:10.1038/s41586-020-2179-y · Cited by 3,661 · see citing works
Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle
Lu, H., Stratton, C. W., & Tang, Y. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25678 · Cited by 3,497 · see citing works
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., McCullough, M. P., Chappell, J. D., Denison, M. R., Stevens, L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022483 · Cited by 3,237 · see citing works
RNA-Based COVID-19 Vaccine BNT162b2 Selected for a Pivotal Efficacy Study
Walsh, E. E., Frenck, R., Falsey, A. R., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Mulligan, M. J., Bailey, R., et al. (2020) · doi:10.1101/2020.08.17.20176651 · Cited by 2,615 · see citing works
Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.022 · Cited by 1,852 · see citing works
Coutard, B., Valle, C., de Lamballerie, X. N., Canard, B., Seidah, N. G., & Decroly, É. (2020) · Antiviral Research · doi:10.1016/j.antiviral.2020.104742 · Cited by 1,685 · see citing works
SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness
Corbett, K. S., Edwards, D. K., Leist, S. R., Abiona, O. M., Boyoglu-Barnum, S., Gillespie, R. A., Himansu, S., Schäfer, A., Ziwawo, C. T., DiPiazza, A. T., et al. (2020) · Nature · doi:10.1038/s41586-020-2622-0 · Cited by 1,615 · see citing works
Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Raabe, V., Bailey, R., Swanson, K. A., et al. (2020) · doi:10.1101/2020.06.30.20142570 · Cited by 1,569 · see citing works
Development of an inactivated vaccine candidate for SARS-CoV-2
Gao, Q., Bao, L., Mao, H., Wang, L., Xu, K., Yang, M., Li, Y., Zhu, L., Wang, N., Lv, Z., et al. (2020) · Science · doi:10.1126/science.abc1932 · Cited by 1,434 · see citing works
Seow, J., Graham, C., Merrick, B., Acors, S., Pickering, S., Steel, K. J. A., Hemmings, O., O’Byrne, A., Kouphou, N., Galao, R. P., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-00813-8 · Cited by 1,419 · see citing works
Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
Hsieh, C.-L., Goldsmith, J. A., Schaub, J. M., DiVenere, A. M., Kuo, H.-C., Javanmardi, K., Le, K. C., Wrapp, D., Lee, A. G., Liu, Y., et al. (2020) · Science · doi:10.1126/science.abd0826 · Cited by 1,303 · see citing works
Distinct conformational states of SARS-CoV-2 spike protein
Cai, Y., Zhang, J., Xiao, T., Peng, H., Sterling, S. M., Walsh, R. M., Rawson, S., Rits-Volloch, S., & Chen, B. (2020) · Science · doi:10.1126/science.abd4251 · Cited by 1,221 · see citing works
Self-citationStructures and distributions of SARS-CoV-2 spike proteins on intact virions
Ke, Z., Otón, J., Qu, K., Cortese, M., Žíla, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C. J., Cerikan, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2665-2 · Cited by 1,114 · see citing works
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen
Pallesen, J., Wang, N., Corbett, K. S., Wrapp, D., Kirchdoerfer, R. N., Turner, H. L., Cottrell, C. A., Becker, M. M., Wang, L., Shi, W., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1707304114 · Cited by 1,073 · see citing works
Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates
Corbett, K. S., Flynn, B., Foulds, K. E., Francica, J. R., Boyoglu-Barnum, S., Werner, A. P., Flach, B., O’Connell, S., Bock, K. W., Minai, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2024671 · Cited by 1,066 · see citing works
DNA vaccine protection against SARS-CoV-2 in rhesus macaques
Yu, J., Tostanoski, L. H., Peter, L., Mercado, N. B., McMahan, K., Mahrokhian, S. H., Nkolola, J. P., Liu, J., Li, Z., Chandrashekar, A., et al. (2020) · Science · doi:10.1126/science.abc6284 · Cited by 997 · see citing works
Single-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques
Mercado, N. B., Zahn, R., Wegmann, F., Loos, C., Chandrashekar, A., Yu, J., Liu, J., Peter, L., McMahan, K., Tostanoski, L. H., et al. (2020) · Nature · doi:10.1038/s41586-020-2607-z · Cited by 789 · see citing works
Rapid COVID-19 vaccine development
Graham, B. S. (2020) · Science · doi:10.1126/science.abb8923 · Cited by 771 · see citing works
Pre-fusion structure of a human coronavirus spike protein
Kirchdoerfer, R. N., Cottrell, C. A., Wang, N., Pallesen, J., Yassine, H. M., Turner, H. L., Corbett, K. S., Graham, B. S., McLellan, J. S., & Ward, A. B. (2016) · Nature · doi:10.1038/nature17200 · Cited by 765 · see citing works
Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins
Xiao, K., Zhai, J., Feng, Y., Zhou, N., Zhang, X., Zou, J.-J., Li, N., Guo, Y., Li, X., Shen, X., et al. (2020) · Nature · doi:10.1038/s41586-020-2313-x · Cited by 728 · see citing works
Crawford, K. H. D., Eguia, R. T., Dingens, A. S., Loes, A. N., Malone, K. D., Wolf, C. R., Chu, H. Y., Tortorici, M. A., Veesler, D., Murphy, M., et al. (2020) · Viruses · doi:10.3390/v12050513 · Cited by 727 · see citing works
Helmy, Y. A., Fawzy, M., Elaswad, A., Sobieh, A., Kenney, S. P., & Shehata, A. A. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041225 · Cited by 687 · see citing works
mRNA vaccine delivery using lipid nanoparticles
Reichmuth, A. M., Oberli, M. A., Jaklenec, A., Langer, R., & Blankschtein, D. (2016) · Therapeutic Delivery · doi:10.4155/tde-2016-0006 · Cited by 624 · see citing works
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies
Wrapp, D., De Vlieger, D., Corbett, K. S., Torres, G. M., Wang, N., Van Breedam, W., Roose, K., van Schie, L., Hoffmann, M., Pöhlmann, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.031 · Cited by 610 · see citing works
SARS-CoV-2, SARS-CoV, and MERS-COV: A comparative overview
Rabaan, A. A., Al-Ahmed, S. H., Haque, S., Sah, R., Tiwari, R., Malik, Y. S., Dhama, K., Yatoo, M. I., Bonilla‐Aldana, D. K., & Rodriguez-Morales, A. J. (2020) · PubMed · Cited by 592 · see citing works
Tseng, C.-T. K., Sbrana, E., Iwata‐Yoshikawa, N., Newman, P. C., Garron, T. M., Atmar, R. L., Peters, C. J., & Couch, R. B. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035421 · Cited by 555 · see citing works
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0468-7 · Cited by 544 · see citing works
Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer
Walls, A. C., Tortorici, M. A., Bosch, B., Frenz, B., Rottier, P. J. M., DiMaio, F., Rey, F. A., & Veesler, D. (2016) · Nature · doi:10.1038/nature16988 · Cited by 539 · see citing works
Bolles, M., Deming, D., Long, K., Agnihothram, S., Whitmore, A., Ferris, M., Funkhouser, W., Gralinski, L., Totura, A., Heise, M., et al. (2011) · Journal of Virology · doi:10.1128/jvi.06048-11 · Cited by 477 · see citing works
McKay, P. F., Hu, K., Blakney, A. K., Samnuan, K., Brown, J. C., Penn, R., Zhou, J., Bouton, C. R., Rogers, P., Polra, K., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17409-9 · Cited by 462 · see citing works
Longitudinal evaluation and decline of antibody responses in SARS-CoV-2 infectionPreprint
Seow, J., Graham, C., Merrick, B., Acors, S., Steel, K., Hemmings, O., O'Bryne, A., Kouphou, N., Pickering, S., Rui, G.-L. P., et al. (2020) · medRxiv · doi:10.1101/2020.07.09.20148429 · Cited by 411 · see citing works
Furin‐mediated protein processing in infectious diseases and cancer
Braun, E., & Sauter, D. (2019) · Clinical & Translational Immunology · doi:10.1002/cti2.1073 · Cited by 345 · see citing works
Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike
Huo, J., Zhao, Y., Ren, J., Zhou, D., Duyvesteyn, H. M. E., Ginn, H. M., Carrique, L., Malinauskas, T., Ruza, R. R., Shah, P. N. M., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.06.010 · Cited by 317 · see citing works
A model of the ACE2 structure and function as a SARS-CoV receptor
Prabakaran, P., Xiao, X., & Dimitrov, D. S. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.12.081 · Cited by 209 · see citing works
SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen PreparednessPreprint
Corbett, K. S., Edwards, D. K., Leist, S. R., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.11.145920 · Cited by 143 · see citing works
Wang, S., Guo, F., Liu, K., Wang, H., Rao, S., Yang, P., & Jiang, C. (2008) · Virus Research · doi:10.1016/j.virusres.2008.03.004 · Cited by 134 · see citing works
Falloon, J., Yu, J. H., Esser, M. T., Villafana, T. L., Li, Y., Dubovsky, F., Takas, T., Levin, M. J., & Falsey, A. R. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jix503 · Cited by 131 · see citing works
Kaul, D. (2020) · Current Medicine Research and Practice · doi:10.1016/j.cmrp.2020.04.001 · Cited by 113 · see citing works
DeRosa, F., Smith, L., Shen, Y., Huang, Y., Pan, J., Xie, H., Yahalom, B., & Heartlein, M. W. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.03.001 · Cited by 111 · see citing works
Self-citationThe SARS-CoV-2 Coronavirus and the COVID-19 Outbreak
Lauxmann, M. A., Santucci, N. E., & Autrán-Gómez, A. M. (2020) · International braz j urol · doi:10.1590/s1677-5538.ibju.2020.s101 · Cited by 106 · see citing works
Peacock, T. P., Goldhill, D. H., Zhou, J., Baillon, L., Frise, R., Swann, O. C., Kugathasan, R., Penn, R., Brown, J. C., Sanchez-David, R. Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.30.318311 · Cited by 88 · see citing works
COVID-19: Time to exonerate the pangolin from the transmission of SARS-CoV-2 to humans
Frutos, R., Cobo, J. S., Chen, T., & Devaux, C. A. (2020) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2020.104493 · Cited by 87 · see citing works
Nelson, C. S., Jenks, J. A., Pardi, N., Goodwin, M. L., Roark, H. K., Edwards, W., McLellan, J. S., Pollara, J., Weissman, D., & Permar, S. R. (2020) · Journal of Virology · doi:10.1128/jvi.00186-20 · Cited by 60 · see citing works
A Cryptic Site of Vulnerability on the Receptor Binding Domain of the SARS-CoV-2 Spike GlycoproteinPreprint
Joyce, M. G., Sankhala, R. S., Chen, W., Choe, M., Bai, H., Hajduczki, A., Yan, L., Sterling, S. L., Peterson, C. E., Green, E. C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.15.992883 · Cited by 47 · see citing works
Natural Polymorphisms Are Present in the Furin Cleavage Site of the SARS-CoV-2 Spike Glycoprotein
Xing, Y., Li, X., Gao, X., & Dong, Q. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00783 · Cited by 41 · see citing works
Kroemer, M., Spehner, L., Vettoretti, L., Bouard, A., Eberst, G., Pili‐Floury, S., Capellier, G., Lepiller, Q., Orillard, É., Mansi, L., et al. (2020) · Journal of Infection · doi:10.1016/j.jinf.2020.08.036 · Cited by 35 · see citing works
Stefano, M. L., Kream, R. M., & Stefano, G. B. (2020) · Medical Science Monitor · doi:10.12659/msm.926016 · Cited by 26 · see citing works
Wrobel, A. G., Benton, D. J., Xu, P., Roustan, C., Martin, S. R., Rosenthal, P. B., Skehel, J. J., & Gamblin, S. J. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0509-2 · Cited by 22 · see citing works
[Progress and challenge of vaccine development against 2019-novel coronavirus (2019-nCoV)].
Shi, Y., Wang, N., & Zou, Q. (2020) · PubMed · doi:10.3760/cma.j.cn112150-20200317-00366 · Cited by 21 · see citing works
Recent Trends in RSV Immunoprophylaxis: Clinical Implications for the Infant
Acero‐Bedoya, S., Wozniak, P. S., Sánchez, P. J., et al. (2019) · American Journal of Perinatology · doi:10.1055/s-0039-1691803 · Cited by 16 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Sambrook, J. & Russel, D. W. Molecular cloning. Laboratory manual. Third Edition edn, Vol. 1 (Cold Spring Harbor Laboratory Press, 2001).
Cited by
Sorted by citations
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
Nanomaterial Delivery Systems for mRNA Vaccines
Buschmann, M. D., Carrasco, M. J., Alishetty, S., Paige, M., Alameh, M. G., & Weissman, D. (2021) · Vaccines · doi:10.3390/vaccines9010065 · Cited by 582 · see citing works
Rauch, S., Roth, N., Schwendt, K., Fotin-Mleczek, M., Mueller, S. O., & Petsch, B. (2021) · npj Vaccines · doi:10.1038/s41541-021-00311-w · Cited by 165 · see citing works
- Authors
- Kalnin, K. V., Plitnik, T., Kishko, M., Zhang, J., Zhang, D., Beauvais, A., Anosova, N. G., Tibbitts, T., DiNapoli, J. M., Huang, P.-W. D., Huleatt, J., Vincent, D., Fries, K., Karve, S., Goldman, R., Gopani, H., Dias, A., Tran, K., Zacharia, M., Gu, X., Boeglin, L., Chivukula, S., Swearingen, R., Landolfi, V., Fu, T.-M., DeRosa, F., & Casimiro, D.
- Affiliations
- Translate Bio (United States) (US)
- Corresponding author
- Kalnin, Kirill V.
- ORCID
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2020-10-14
- OpenAlex
- W3092716386
- Cited by
- 18
- References
- 53
- Citations by year
- 2023: 1 · 2022: 2 · 2021: 13 · 2020: 2
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, other-oa)
- Funders
- Sanofi
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- mRNA vaccines, COVID-19 vaccines, SARS-CoV-2 spike protein, neutralizing antibodies, T helper 1 response, immunogenicity, cynomolgus macaques, dose-ranging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
