Cited by 30

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19: Protection of mice after a single immunization

Hennrich, Alexandru A., Sawatsky, Bevan, Santos-Mandujano, Rosalía, Banda, Dominic H., Oberhuber, Martina, Schopf, Anika, Pfaffinger, Verena, Wittwer, Kevin, Riedel, Christiane, Pfaller, Christian K., Conzelmann, Karl-Klaus·2021·PLOS Pathogens

Abstract

Vaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine complemented with VSV G, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients, and protected transgenic K18-hACE2 mice from COVID-19-like disease. Homologous boost immunization further enhanced virus neutralizing activity. The results demonstrate that non-spreading rhabdovirus RNA replicons expressing minispike proteins represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.

Overview

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.ppat.1009064

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Verification

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.

A few free checks a day · papers already verified open instantly · results are public

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Show all 14 references

Research works printed but not linked: 87

  1. KS Corbett, 2020, SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness, Nature
  2. WS Lee, 2020, Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies, Nature microbiology
  3. M Jeyanathan, 2020, Immunological considerations for COVID-19 vaccine strategies, Nat Rev Immunol
  4. M Cloutier, 2020, ADE and hyperinflammation in SARS-CoV2 infection- comparison with dengue hemorrhagic fever and feline infectious peritonitis, Cytokine, 136, 155256, 10.1016/j.cyto.2020.155256 · DOI
  5. TJ Ruckwardt, 2019, Immunological Lessons from Respiratory Syncytial Virus Vaccine Development, Immunity, 51, 429, 10.1016/j.immuni.2019.08.007 · DOI · Paper page
  6. FP Polack, 2002, A role for immune complexes in enhanced respiratory syncytial virus disease, J Exp Med, 196, 859, 10.1084/jem.20020781 · DOI
  7. PL Acosta, 2015, Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease, Clin Vaccine Immunol, 23, 189, 10.1128/CVI.00609-15 · DOI
  8. F Wu, 2020, A new coronavirus associated with human respiratory disease in China, Nature, 579, 265, 10.1038/s41586-020-2008-3 · DOI · Paper page
  9. P Zhou, 2020, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, 579, 270, 10.1038/s41586-020-2012-7 · DOI · Paper page
  10. N Zhu, 2020, A Novel Coronavirus from Patients with Pneumonia in China, 2019, The New England journal of medicine, 382, 727, 10.1056/NEJMoa2001017 · DOI · Paper page
  11. TG Ksiazek, 2003, A novel coronavirus associated with severe acute respiratory syndrome, N Engl J Med, 348, 1953, 10.1056/NEJMoa030781 · DOI
  12. C Drosten, 2003, Identification of a novel coronavirus in patients with severe acute respiratory syndrome, The New England journal of medicine, 348, 1967, 10.1056/NEJMoa030747 · DOI · Paper page
  13. UJ Buchholz, 2004, Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity, Proc Natl Acad Sci U S A, 101, 9804, 10.1073/pnas.0403492101 · DOI
  14. K McMahan, 2020, Correlates of protection against SARS-CoV-2 in rhesus macaques, Nature
  15. Z Wang, 2021, mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants, Nature
  16. MS Suthar, 2020, Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients, Cell reports Medicine, 1, 100040, 10.1016/j.xcrm.2020.100040 · DOI · Paper page
  17. C Atyeo, 2021, Dissecting strategies to tune the therapeutic potential of SARS-CoV-2-specific monoclonal antibody CR3022, JCI insight., 6, 10.1172/jci.insight.143129 · DOI
  18. SJ Zost, 2020, Potently neutralizing and protective human antibodies against SARS-CoV-2, Nature
  19. D Bestle, 2020, TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells, Life science alliance, 3, 10.26508/lsa.202000786 · DOI · Paper page
  20. M Hoffmann, 2020, SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor, Cell
  21. J Lan, 2020, Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor, Nature, 581, 215, 10.1038/s41586-020-2180-5 · DOI · Paper page
  22. D Wrapp, 2020, Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science, 367, 1260, 10.1126/science.abb2507 · DOI · Paper page
  23. YI Kim, 2020, Infection and Rapid Transmission of SARS-CoV-2 in Ferrets, Cell host & microbe
  24. J Shi, 2020, Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2, Science
  25. C Kreer, 2020, Longitudinal Isolation of Potent Near-Germline SARS-CoV-2-Neutralizing Antibodies from COVID-19, Patients. Cell
  26. Y Cao, 2020, Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients’ B Cells, Cell, 182, 73, 10.1016/j.cell.2020.05.025 · DOI · Paper page
  27. Q Wang, 2016, Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates, ACS infectious diseases, 2, 361, 10.1021/acsinfecdis.6b00006 · DOI
  28. D Li, 2021, The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman primates, bioRxiv: the preprint server for biology
  29. W Hoepel, 2020, Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses, bioRxiv: the preprint server for biology
  30. ND Lawson, 1995, Recombinant vesicular stomatitis viruses from DNA, Proc Natl Acad Sci U S A, 92, 4477, 10.1073/pnas.92.10.4477 · DOI
  31. MJ Schnell, 1994, Infectious rabies viruses from cloned cDNA, EMBO J, 13, 4195, 10.1002/j.1460-2075.1994.tb06739.x · DOI
  32. F Zemp, 2018, Rhabdoviruses as vaccine platforms for infectious disease and cancer, Biotechnology & genetic engineering reviews, 34, 122, 10.1080/02648725.2018.1474320 · DOI
  33. MK Melzer, 2017, Oncolytic Vesicular Stomatitis Virus as a Viro-Immunotherapy: Defeating Cancer with a "Hammer" and "Anvil", Biomedicines., 5, 10.3390/biomedicines5010008 · DOI
  34. SU Kapadia, 2008, SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector, Virology, 376, 165, 10.1016/j.virol.2008.03.002 · DOI
  35. SU Kapadia, 2005, Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine, Virology, 340, 174, 10.1016/j.virol.2005.06.016 · DOI
  36. A Roberts, 1999, Attenuated vesicular stomatitis viruses as vaccine vectors, J Virol, 73, 3723, 10.1128/JVI.73.5.3723-3732.1999 · DOI
  37. KM Matz, 2019, Ebola vaccine trials: progress in vaccine safety and immunogenicity, Expert review of vaccines, 18, 1229, 10.1080/14760584.2019.1698952 · DOI
  38. JB Case, 2020, Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2, Cell host & microbe
  39. ME Dieterle, 2020, A Replication-Competent Vesicular Stomatitis Virus for Studies of SARS-CoV-2 Spike-Mediated Cell Entry and Its Inhibition, Cell host & microbe
  40. Y Yahalom-Ronen, 2020, A single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge, Nature communications., 11, 6402, 10.1038/s41467-020-20228-7 · DOI
  41. W Furuyama, 2021, Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a recombinant vaccine, bioRxiv: the preprint server for biology
  42. S Fukushi, 2006, Evaluation of a novel vesicular stomatitis virus pseudotype-based assay for detection of neutralizing antibody responses to SARS-CoV, Journal of medical virology, 78, 1509, 10.1002/jmv.20732 · DOI
  43. Y Yahalom-Ronen, 2020, A single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge, bioRxiv: the preprint server for biology
  44. Y Weisblum, 2020, Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants, eLife, 9, 10.7554/eLife.61312 · DOI · Paper page
  45. AN van den Pol, 2017, Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain, J Virol, 91, 10.1128/JVI.02154-16 · DOI
  46. J Shang, 2020, Structural basis of receptor recognition by SARS-CoV-2, Nature
  47. R Yan, 2020, Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2, Science, 367, 1444, 10.1126/science.abb2762 · DOI
  48. AC Walls, 2020, Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein, Cell, 181, 281, 10.1016/j.cell.2020.02.058 · DOI · Paper page
  49. Y Klingen, 2008, Double-labeled rabies virus: live tracking of enveloped virus transport, JVirol, 82, 237, 10.1128/JVI.01342-07 · DOI
  50. MJ Schnell, 1998, Requirement for a non-specific glycoprotein cytoplasmic domain sequence to drive efficient budding of vesicular stomatitis virus, Embo j, 17, 1289, 10.1093/emboj/17.5.1289 · DOI
  51. T Mebatsion, 1997, A CXCR4/CD4 pseudotype rhabdovirus that selectively infects HIV-1 envelope protein-expressing cells, Cell, 90, 841, 10.1016/S0092-8674(00)80349-9 · DOI
  52. M Yuan, 2020, A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and, SARS-CoV. Science
  53. KK Conzelmann, 1998, Nonsegmented negative-strand RNA viruses: genetics and manipulation of viral genomes, AnnuRev Genet, 32, 123, 10.1146/annurev.genet.32.1.123 · DOI
  54. EB Flanagan, 2000, Moving the glycoprotein gene of vesicular stomatitis virus to promoter-proximal positions accelerates and enhances the protective immune response, J Virol, 74, 7895, 10.1128/JVI.74.17.7895-7902.2000 · DOI
  55. A Hanika, 2005, Use of influenza C virus glycoprotein HEF for generation of vesicular stomatitis virus pseudotypes, J Gen Virol, 86, 1455, 10.1099/vir.0.80788-0 · DOI
  56. A Ghanem, 2012, Significantly improved rescue of rabies virus from cDNA plasmids, EurJCell Biol, 91, 10
  57. A Ghanem, 2016, G gene-deficient single-round rabies viruses for neuronal circuit analysis, Virus Res, 216, 41, 10.1016/j.virusres.2015.05.023 · DOI
  58. UJ Buchholz, 1999, Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter, J Virol, 73, 251, 10.1128/JVI.73.1.251-259.1999 · DOI
  59. Y Gaudin, 1992, Rabies virus glycoprotein is a trimer, Virology, 187, 627, 10.1016/0042-6822(92)90465-2 · DOI
  60. DS Lyles, 1992, Subunit interactions of vesicular stomatitis virus envelope glycoprotein stabilized by binding to viral matrix protein, J Virol, 66, 349, 10.1128/JVI.66.1.349-358.1992 · DOI
  61. P Zagouras, 1993, Dynamic equilibrium between vesicular stomatitis virus glycoprotein monomers and trimers in the Golgi and at the cell surface, J Virol, 67, 7533, 10.1128/JVI.67.12.7533-7538.1993 · DOI
  62. T Mebatsion, 1996, Budding of rabies virus particles in the absence of the spike glycoprotein, Cell, 84, 941, 10.1016/S0092-8674(00)81072-7 · DOI
  63. AA Albertini, 2012, Characterization of Monomeric Intermediates during VSV Glycoprotein Structural Transition, PLOS Pathogens, 8, e1002556, 10.1371/journal.ppat.1002556 · DOI
  64. MM Rolls, 1994, Novel infectious particles generated by expression of the vesicular stomatitis virus glycoprotein from a self-replicating RNA, Cell, 79, 497, 10.1016/0092-8674(94)90258-5 · DOI
  65. P-E Mangeot, 2011, Protein Transfer Into Human Cells by VSV-G-induced Nanovesicles, Molecular Therapy, 19, 1656, 10.1038/mt.2011.138 · DOI
  66. CK Yinda, 2021, K18-hACE2 mice develop respiratory disease resembling severe COVID-19, PLoS Pathog., 17, e1009195, 10.1371/journal.ppat.1009195 · DOI
  67. W Dejnirattisai, 2021, The antigenic anatomy of SARS-CoV-2 receptor binding domain, Cell
  68. X Chi, 2020, A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2, Science, 369, 650, 10.1126/science.abc6952 · DOI · Paper page
  69. N Suryadevara, 2021, Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein, Cell
  70. L Dai, 2020, A Universal Design of Betacoronavirus Vaccines against COVID-19, MERS, and SARS, Cell., 182, 722, 10.1016/j.cell.2020.06.035 · DOI
  71. MJ Mulligan, 2020, Phase 1/2 study of COVID-19 RNA vaccine BNT162b1 in adults, Nature
  72. Y Yang, 2021, Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses, Vaccines., 9, 10.3390/vaccines9020073 · DOI
  73. LM Grobbelaar, 2021, SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID-19, medRxiv: the preprint server for health sciences.
  74. D Wrapp, 2020, Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies, Cell
  75. L Sissoeff, 2005, Stable trimerization of recombinant rabies virus glycoprotein ectodomain is required for interaction with the p75NTR receptor, J Gen Virol, 86, 2543, 10.1099/vir.0.81063-0 · DOI
  76. C Riedel, 2019, Cryo EM structure of the rabies virus ribonucleoprotein complex, Scientific reports, 9, 9639, 10.1038/s41598-019-46126-7 · DOI
  77. T Mebatsion, 1999, Matrix protein of rabies virus is responsible for the assembly and budding of bullet-shaped particles and interacts with the transmembrane spike glycoprotein G, J Virol, 73, 242, 10.1128/JVI.73.1.242-250.1999 · DOI
  78. E Szomolanyi-Tsuda, 1998, T-cell-independent antiviral antibody responses, Current opinion in immunology, 10, 431, 10.1016/S0952-7915(98)80117-9 · DOI
  79. MF Bachmann, 1995, T helper cell-independent neutralizing B cell response against vesicular stomatitis virus: role of antigen patterns in B cell induction?, European journal of immunology, 25, 3445, 10.1002/eji.1830251236 · DOI
  80. A Roldão, 2010, Virus-like particles in vaccine development, Expert review of vaccines, 9, 1149, 10.1586/erv.10.115 · DOI
  81. EK Bongiorno, 2017, Type 1 Immune Mechanisms Driven by the Response to Infection with Attenuated Rabies Virus Result in Changes in the Immune Bias of the Tumor Microenvironment and Necrosis of Mouse GL261, Brain Tumors. J Immunol, 198, 4513
  82. M De Giovanni, 2020, Spatiotemporal regulation of type I interferon expression determines the antiviral polarization of CD4(+) T cells, Nat Immunol., 21, 321, 10.1038/s41590-020-0596-6 · DOI
  83. S Finke, 2003, Rabies virus matrix protein regulates the balance of virus transcription and replication, J Gen Virol, 84, 1613, 10.1099/vir.0.19128-0 · DOI
  84. KM Schuhmann, 2011, The measles virus V protein binds to p65 (RelA) to suppress NF-kappaB activity, JVirol., 85, 3162, 10.1128/JVI.02342-10 · DOI
  85. JR Kremer, 1996, Computer Visualization of Three-Dimensional Image Data Using IMOD, Journal of structural biology, 116, 71, 10.1006/jsbi.1996.0013 · DOI
  86. EF Pettersen, 2004, UCSF Chimera—a visualization system for exploratory research and analysis, Journal of computational chemistry, 25, 1605, 10.1002/jcc.20084 · DOI
  87. PB McCray, 2007, Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus, J Virol, 81, 813, 10.1128/JVI.02012-06 · DOI · Paper page

Cited by

Sorted by citations

See all 30

Metadata

Authors
Hennrich, A. A., Sawatsky, B., Santos-Mandujano, R., Banda, D. H., Oberhuber, M., Schopf, A., Pfaffinger, V., Wittwer, K., Riedel, C., Pfaller, C. K., & Conzelmann, K.-K.
Venue
PLOS Pathogens
Published
2021-04-21
Volume
17
Issue
4
Pages
e1009064
ISSN
1553-7374
Cited by
30
References
14
Language
en
Funders
  • DFG (DFG Project-ID 369799452 - TRR237 A12, DFG Project-ID 118803580 - SFB 870 Z1, DFG SFB 1021 project ID 197785619/B12)
  • LMU Munich (FöFoLe M 09/2017)
  • German Federal Ministry of Health
  • Deutsches Zentrum für Infektionsforschung (HZI2016Z9)

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