CoChat
Sign Up
Cited by 601SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections Studiesvaccines and immunoinformatics approaches

Immunogenicity of a DNA vaccine candidate for COVID-19

Open access
Smith, Trevor R. F., Patel, Ami, Ramos, Stephanie, Elwood, Dustin, Zhu, Xizhou, Yan, Jian, Gary, Ebony N., Walker, Susanne N. +51 more·2020·Nature Communications
DOI 10.1038/s41467-020-16505-0PMC PMC7239918

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.

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 · 10.1038/s41467-020-16505-0

Cites

2 of 2 references verified0 citation errors · 0 not checkable

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.

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?

  • The S glycoprotein is the primary vaccine target for many candidate SARS-CoV-2 vaccines.

    “The S glycoprotein mediates host cell attachment and is required for viral entry3; it is the primary vaccine target for many candidate SARS-CoV-2 vaccines.4-7”

    From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [7]

    The Discussion says the authors chose SARS-CoV-2 S protein as the antigen target for their vaccine candidate, and the Results describe constructs encoding it. Our copy does not establish that S is the primary target for many SARS-CoV-2 vaccine candidates, so the broader claim is not fully supported. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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

Flagged first, then by citations

Research works printed but not linked: 41

  1. [1]Zhu V A Novel Coronavirus from Patients with Pneumonia in China, 2019 N. Engl. J. Med. 2020 382 727 733 10.1056/NEJMoa2001017 31978945 PMC7092803 · DOI · Paper page
  2. [3]Huang C Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China Lancet 2020 395 497 506 10.1016/S0140-6736(20)30183-5 31986264 PMC7159299 · DOI · Paper page
  3. [6]Hulkower RL Casanova LM Rutala WA Weber DJ Sobsey MD Inactivation of surrogate coronaviruses on hard surfaces by health care germicides Am. J. Infect. Control 2011 39 401 407 10.1016/j.ajic.2010.08.011 21256627 PMC7132663 · DOI
  4. [7]Tebas P Intradermal SynCon(R) Ebola GP DNA vaccine is temperature stable and safely demonstrates cellular and humoral immunogenicity advantages in healthy volunteers J. Infect. Dis. 2019 220 400 410 10.1093/infdis/jiz132 30891607 · DOI
  5. [8]Yang ZY A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice Nature 2004 428 561 564 10.1038/nature02463 15024391 PMC7095382 · DOI
  6. [9]Modjarrad K Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial Lancet Infect. Dis. 2019 19 1013 1022 10.1016/S1473-3099(19)30266-X 31351922 PMC7185789 · DOI
  7. [10]Muthumani K A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates Sci. Transl. Med. 2015 7 301ra132 10.1126/scitranslmed.aac7462 PMC4573558 26290414 · DOI
  8. [11]Tebas, P. et al. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report. N. Engl. J. Med.10.1056/NEJMoa1708120 (2017). PMC6824915 34525286 · DOI
  9. [13]Kirchdoerfer RN Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis Sci. Rep. 2018 8 15701 10.1038/s41598-018-34171-7 30356097 PMC6200764 · DOI · Paper page
  10. [14]Wang, L. et al. Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on the Middle East respiratory syndrome coronavirus spike glycoprotein to avoid neutralization escape. J. Virol.92, e02002-17 (2018). PMC5923077 29514901
  11. [15]Tian X Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody Emerg. Microbes Infect. 2020 9 382 385 10.1080/22221751.2020.1729069 32065055 PMC7048180 · DOI
  12. [16]Sardesai NY Weiner DB Electroporation delivery of DNA vaccines: prospects for success Curr. Opin. Immunol. 2011 23 421 429 10.1016/j.coi.2011.03.008 21530212 PMC3109217 · DOI · Paper page
  13. [17]Carter D The adjuvant GLA-AF enhances human intradermal vaccine responses Sci. Adv. 2018 4 eaas9930 10.1126/sciadv.aas9930 30221194 PMC6136895 · DOI
  14. [18]Schultheis K Characterization of guinea pig T cell responses elicited after EP-assisted delivery of DNA vaccines to the skin Vaccine 2017 35 61 70 10.1016/j.vaccine.2016.11.052 27894716 PMC5221502 · DOI
  15. [19]Rosen O A high-throughput inhibition assay to study MERS-CoV antibody interactions using image cytometry J. Virol. Methods 2019 265 77 83 10.1016/j.jviromet.2018.11.009 30468747 PMC6357230 · DOI
  16. [20]Ahmed S Quadeer AA McKay MR Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies Viruses 2020 12 254 10.3390/v12030254 PMC7150947 32106567 · DOI
  17. [21]Patel A Protective efficacy and long-term immunogenicity in cynomolgus macaques by Ebola virus glycoprotein synthetic DNA vaccines J. Infect. Dis. 2019 219 544 555 10.1093/infdis/jiy537 30304515 · DOI
  18. [22]Jiang J Immunogenicity of a protective intradermal DNA vaccine against lassa virus in cynomolgus macaques Hum. Vaccin Immunother. 2019 15 2066 2074 10.1080/21645515.2019.1616499 31071008 PMC6773375 · DOI
  19. [23]Zhou P A pneumonia outbreak associated with a new coronavirus of probable bat origin Nature 2020 579 270 273 10.1038/s41586-020-2012-7 32015507 PMC7095418 · DOI · Paper page
  20. [24]Zhu Z Potent cross-reactive neutralization of SARS coronavirus isolates by human monoclonal antibodies Proc. Natl Acad. Sci. USA 2007 104 12123 12128 10.1073/pnas.0701000104 17620608 PMC1924550 · DOI
  21. [25]He Y Identification of a critical neutralization determinant of severe acute respiratory syndrome (SARS)-associated coronavirus: importance for designing SARS vaccines Virology 2005 334 74 82 10.1016/j.virol.2005.01.034 15749124 PMC7111853 · DOI
  22. [26]Zhao Jingxian Alshukairi Abeer N. Baharoon Salim A. Ahmed Waleed A. Bokhari Ahmad A. Nehdi Atef M. Layqah Laila A. Alghamdi Mohammed G. Al Gethamy Manal M. Dada Ashraf M. Khalid Imran Boujelal Mohamad Al Johani Sameera M. Vogel Leatrice Subbarao Kanta Mangalam Ashutosh Wu Chaorong Ten Eyck Patrick Perlman Stanley Zhao Jincun Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses Science Immunology 2017 2 14 eaan5393 10.1126/sciimmunol.aan5393 28778905 PMC5576145 · DOI
  23. [27]Janice Oh HL Ken-En Gan S Bertoletti A Tan YJ Understanding the T cell immune response in SARS coronavirus infection Emerg. Microbes Infect. 2012 1 e23 10.1038/emi.2012.26 26038429 PMC3636424 · DOI
  24. [28]Tseng CT Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus PLoS ONE 2012 7 e35421 10.1371/journal.pone.0035421 22536382 PMC3335060 · DOI
  25. [29]Iwata-Yoshikawa N Effects of Toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine J. Virol. 2014 88 8597 8614 10.1128/JVI.00983-14 24850731 PMC4135953 · DOI
  26. [30]Bolles M A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge J. Virol. 2011 85 12201 12215 10.1128/JVI.06048-11 21937658 PMC3209347 · DOI · Paper page
  27. [31]Yasui F Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV J. Immunol. 2008 181 6337 6348 10.4049/jimmunol.181.9.6337 18941225 · DOI
  28. [32]Wang Q Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates ACS Infect. Dis. 2016 2 361 376 10.1021/acsinfecdis.6b00006 27627203 PMC7075522 · DOI
  29. [33]Agrawal AS Immunization with inactivated Middle East Respiratory Syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus Hum. Vaccin Immunother. 2016 12 2351 2356 10.1080/21645515.2016.1177688 27269431 PMC5027702 · DOI
  30. [34]Luo F Evaluation of antibody-dependent enhancement of SARS-CoV infection in Rhesus Macaques immunized with an inactivated SARS-CoV vaccine Virol. Sin. 2018 33 201 204 10.1007/s12250-018-0009-2 29541941 PMC6178114 · DOI
  31. [35]Qin E Immunogenicity and protective efficacy in monkeys of purified inactivated Vero-cell SARS vaccine Vaccine 2006 24 1028 1034 10.1016/j.vaccine.2005.06.038 16388880 PMC7115602 · DOI
  32. [36]Roberts A Immunogenicity and protective efficacy in mice and hamsters of a beta-propiolactone inactivated whole virus SARS-CoV vaccine Viral Immunol. 2010 23 509 519 10.1089/vim.2010.0028 20883165 PMC2967819 · DOI
  33. [37]Deng Y Enhanced protection in mice induced by immunization with inactivated whole viruses compare to spike protein of middle east respiratory syndrome coronavirus Emerg. Microbes Infect. 2018 7 60 10.1038/s41426-018-0056-7 29618723 PMC5884803 · DOI
  34. [38]Zhang N Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus Cell Mol. Immunol. 2016 13 180 190 10.1038/cmi.2015.03 25640653 PMC4786625 · DOI
  35. [39]Luke T Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo Sci. Transl. Med. 2016 8 326ra321 10.1126/scitranslmed.aaf1061 26888429 · DOI
  36. [40]Darnell ME Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets J. Infect. Dis. 2007 196 1329 1338 10.1086/522431 17922397 PMC7110120 · DOI
  37. [41]Smith TRF Development of an intradermal DNA vaccine delivery strategy to achieve single-dose immunity against respiratory syncytial virus Vaccine 2017 35 2840 2847 10.1016/j.vaccine.2017.04.008 28413132 PMC5814302 · DOI
  38. [42]Yan J Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B consensus-based envelope DNA vaccine Mol. Ther. 2007 15 411 421 10.1038/sj.mt.6300036 17235321 · DOI
  39. [43]Bagarazzi ML Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses Sci. Transl. Med. 2012 4 155ra138 10.1126/scitranslmed.3004414 PMC4317299 23052295 · DOI
  40. [44]Caly, L. et al. Isolation and rapid sharing of the 2019 novel coronavirus (SARS-CoV-2) from the first patient diagnosed with COVID-19 in Australia. Med. J. Aust. (2020). PMC7228321 32237278
  41. [45]Huang PS RosettaRemodel: a generalized framework for flexible backbone protein design PLoS ONE 2011 6 e24109 10.1371/journal.pone.0024109 21909381 PMC3166072 · DOI

Cited by

Sorted by citations

Authors
Smith, T. R. F., Patel, A., Ramos, S., Elwood, D., Zhu, X., Yan, J., Gary, E. N., Walker, S. N., Schultheis, K., Purwar, M., Xu, Z., Walters, J., Bhojnagarwala, P., Yang, M., Chokkalingam, N., Pezzoli, P., Parzych, E., Reuschel, E. L., Doan, A., Tursi, N., Vasquez, M., Choi, J., Tello-Ruiz, E., Maricic, I., Bah, M. A., Wu, Y., Amante, D., Park, D. H., Dia, Y., Ali, A. R., Zaidi, F. I., Generotti, A., Kim, K. Y., Herring, T. A., Reeder, S., Andrade, V. M., Buttigieg, K., Zhao, G., Wu, J.-M., Li, D., Bao, L., Liu, J., Deng, W., Qin, C., Brown, A. S., Khoshnejad, M., Wang, N., Chu, J., Wrapp, D., McLellan, J. S., Muthumani, K., Wang, B., Carroll, M. W., Kim, J. J., Boyer, J., Kulp, D. W., Humeau, L. M. P. F., Weiner, D. B., & Broderick, K. E.
Affiliations
  • Inovio Pharmaceuticals (United States) (US)
  • The Wistar Institute (US)
  • Public Health England (GB)
  • Shanghai Medical College of Fudan University (CN)
  • The University of Texas at Austin (US)
Corresponding author
Broderick, Kate E.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-05-20
Volume
11
Issue
1
Pages
2601-2601
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-16505-0
PMC
PMC7239918
OpenAlex
W3025521550
Cited by
601
References
2
Citations by year
2026: 8 · 2025: 26 · 2024: 37 · 2023: 56 · 2022: 103 · 2021: 231 · 2020: 140
FWCI
17.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • INOVIO Pharmaceuticals
  • Coalition for Epidemic Preparedness Innovations
  • National Cancer Institute (T32CA009171)
  • National Institute of Allergy and Infectious Diseases (R01AI127521)
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
COVID-19 pandemic, SARS-CoV-2, DNA vaccine, spike protein, immunogenicity, T cell response, neutralizing antibodies, ACE2 receptor, tissue distribution, lung targeting, vaccine candidate
MeSH terms
Angiotensin-Converting Enzyme 2, COVID-19 Vaccines, Animals, Antigens, Viral, Guinea Pigs, Immunoglobulin G, Peptidyl-Dipeptidase A, Lung, Mice, Inbred BALB C, Viral Vaccines, Coronavirus Infections, Epitope Mapping, Vaccines, DNA, Models, Animal, Mice, Immunity, Humoral, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus, Middle East Respiratory Syndrome Coronavirus

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