Jason McLellan

Source: Wikipedia, the free encyclopedia.
Jason McLellan
NationalityAmerican
Education
Scientific career
Fields
Structural Biology
InstitutionsUniversity of Texas at Austin
Websitewww.mclellanlab.org

Jason S. McLellan is a structural biologist, professor in the Department of Molecular Biosciences and Robert A. Welch Chair in Chemistry at

COVID-19,[4] and respiratory syncytial virus (RSV).[5] McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein,[6][7][8][9] which biotechnology company Moderna used as the basis for the vaccine mRNA-1273,[10][11][12][13] the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S.[14] At least three other vaccines use this modified spike protein: those from Pfizer and BioNTech; Johnson & Johnson and Janssen Pharmaceuticals; and Novavax.[7][15]

SARS-CoV-2 research

McLellan led a team from

The University of Texas at Austin and the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center that produced the first molecular structure, or 3D atomic scale map, of the novel coronavirus’ spike protein, the protein that allows the virus to attach to and infect host cells.[6] The results were published online on February 19, 2020, in Science,[16] one of the world's top academic journals, and was highlighted on the cover of the 13 March 2020 print edition.[17]

The molecular structure provides a blueprint for scientists to learn to disrupt these processes through developing new treatments or vaccines.

LiveScience as saying: "It's a very important step forward and may help in the development of a vaccine against SARS-COV-2."[18] The achievement was also highlighted as an important step towards a vaccine by the director of the National Institutes of Health, Francis Collins, in the NIH Director's Blog.[19]

McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein,[6][7][9] called S-2P or 2P, which biotechnology company Moderna used as the basis for the vaccine candidate mRNA-1273,[10][11][12][13] the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S.[14] The UT Austin and NIH teams filed a joint patent application on the mutated spike protein.[20]

Moderna's vaccine candidate, mRNA-1273, contains the genetic code for the stabilized version of the spike protein.[11] When a person is vaccinated with mRNA-1273, their own cells should theoretically produce these modified spike proteins, triggering their immune systems to develop antibodies against the actual coronavirus.[21]

The SARS-CoV-2 spike protein takes on one shape before entering a cell and another shape after, known as the prefusion and postfusion conformations.[22] Antibodies that recognize spike proteins in the prefusion shape are much more effective at preventing infection than antibodies that recognize spike proteins in the postfusion shape.[22] McLellan—along with his team members Daniel Wrapp and Nianshuang Wang, plus Barney Graham and Kizzmekia Corbett at NIAID's Vaccine Research Center—engineered the spike protein to stay in its initial shape so it can be recognized.[16] This, combined with Moderna's technology that uses messenger RNA to encode information about the virus, allows mRNA-1273 to trigger an immune response in vaccinated subjects.[11]

The stabilized spike protein developed by McLellan and his colleagues forms the basis of three COVID-19 vaccines that received emergency use authorization in the U.S.[7][15]

In May, 2020, he published

Newcastle Disease. This vaccine has the benefit of being easy to grow in chicken eggs, which are the basis of existing Influenza vaccines and are easier for developing nations to produce.[24]

McLellan and his team worked with pharmaceutical company

U.S. Food and Drug Administration in November 2020.[26] In April 2021, the EUA was revoked.[27]

In a separate but related project, McLellan and Daniel Wrapp worked with colleagues at the NIAID Vaccine Research Center and Ghent University to develop an antibody therapy for COVID-19 based on antibodies produced by a Winter (llama), a llama.[28] Initial tests indicate that their antibody blocks viruses that display the SARS-CoV-2 spike protein from infecting cells in culture. They reported their findings in Cell on May 5, 2020.[29] As of May 2020, the team was preparing to conduct preclinical studies in animals such as hamsters or nonhuman primates, with the hopes of next testing in humans.[30]

RSV research

Respiratory syncytial virus (RSV) is a very common, contagious virus that causes infections of the respiratory tract. RSV is the single most common cause of respiratory hospitalization in infants, reinfection remains common throughout the lifetime, and it is an important pathogen in all age groups.[31][32]

McLellan, along with Barney S. Graham and Peter Kwong of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center, spearheaded the development of a protein subunit vaccine against RSV called DS-Cav1.[33] When the work began, McLellan was a postdoctoral researcher at VRC working in Graham's and Kwong's labs.

The

virus' F protein, was developed using structure-based vaccine design.[34][35][36] Structure-based vaccines are developed through a rational design process that uses information about the atomic structure of vulnerable parts of a pathogen to create a synthetic molecule that the human immune system recognizes as pathogenic and creates potent antibodies against.[37][38][39]

In a phase 1 clinical trial, DS-Cav1 was shown to be safe and to elicit "a robust boost in RSV F-specific antibodies and neutralising activity that was sustained above baseline for at least 44 weeks", according to a study published in April 2021 in The Lancet Respiratory Medicine.[40]

The first FDA-approved RSV vaccine, AREXVY (developed by GSK plc), uses a version of this antigen and was approved in May 2023 for adults aged 60 and older by the U.S. Food and Drug Administration (FDA).[41][42][5]

As of October 10, 2022, at least three other companies are testing candidate RSV vaccines based on stabilized prefusion F proteins in older adults in Phase 3 trials: Pfizer, Johnson & Johnson, and Moderna.[43][44][45]

Honors and awards

In 2020, Jason McLellan was one of seven researchers honored with a

COVID-19 research.[28][46] He was the 2020 recipient of the William Prusoff Memorial Award from the International Society for Antiviral Research, which honors a young scientist who has shown excellence in antiviral research and promise for future contributions to the field.[47] Previous honors include the Norman P. Salzman Memorial Award in Virology (2012),[48] the Charles H. Hood Foundation Child Health Research Award (2015),[49] the American Crystallographic Association Etter Early Career Award (2018)[50] and the Viruses Young Investigator in Virology Prize (2019).[51]

The Academy of Medicine, Engineering & Science of Texas awarded McLellan its 2022 Edith and Peter O'Donnell Award in Medicine.

Norman Hackerman Award in Chemical Research,[56] and named a Senior Member of the National Academy of Inventors.[57]

References

  1. ^ "UT CNS Directory: Jason McLellan". University of Texas at Austin College of Natural Sciences. Retrieved 14 Aug 2020.
  2. ^ "Jason S. McLellan". Google Scholar. Retrieved 29 May 2020.
  3. ^ "Powerful tools help scientists find a virus's weak spot". National Geographic. 1 February 2022. Archived from the original on February 2, 2022. Retrieved 2 Feb 2022.
  4. ^ "U.S. Scientists Take Key Step Towards Coronavirus Vaccine". U.S. News & World Report. 19 February 2020. Retrieved 29 May 2020.
  5. ^ a b "FDA-Approved RSV Vaccine Enabled by Work of UT Molecular Biologist". University of Texas at Austin. 4 May 2023. Retrieved 8 May 2023.
  6. ^ a b c "How structural biologists revealed the new coronavirus's structure so quickly". Chemical & Engineering News. 2 May 2020. Retrieved 4 June 2020.
  7. ^ a b c d "The tiny tweak behind COVID-19 vaccines". Chemical & Engineering News. 29 Sep 2020. Retrieved 30 Sep 2020.
  8. Washington Post
    . 6 December 2020. Retrieved 9 Dec 2020.
  9. ^ a b Kramer, Jillian (31 December 2020). "They spent 12 years solving a puzzle. It yielded the first COVID-19 vaccines". National Geographic. Archived from the original on February 20, 2021.
  10. ^
    Washington Post
    . 2 July 2020. Retrieved 2 July 2020.
  11. ^
    WIRED
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  12. ^ a b "The sprint to solve coronavirus protein structures — and disarm them with drugs". Nature. 15 May 2020. Retrieved 29 May 2020.
  13. ^
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  14. ^
    New York Times
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  15. ^ a b "A coronavirus vaccine is on the horizon, thanks to a key discovery by UT researchers". Austin American-Statesman. 10 Aug 2020. Retrieved 13 Aug 2020.
  16. ^
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  17. Science Magazine
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  18. ^
    LiveScience
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  19. ^ "Structural Biology Points Way to Coronavirus Vaccine". National Institutes of Health. 3 March 2020. Retrieved 4 June 2020.
  20. ^ "Prefusion Coronavirus Spike Proteins and Their Use". National Institutes of Health. Retrieved 2 July 2020.
  21. Discover Magazine
    . 20 March 2020. Retrieved 29 May 2020.
  22. ^ a b "What will it take to make an effective vaccine for COVID-19?". Chemical & Engineering News. 17 July 2020. Retrieved 13 Aug 2020.
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  24. ^ Zimmer, Carl. "Researchers Are Hatching a Low-Cost Coronavirus Vaccine". Retrieved April 4, 2021.
  25. bioRxiv 10.1101/2020.09.30.318972
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  26. U.S. Food and Drug Administration
    (Press release). 9 Nov 2020. Retrieved 4 Jan 2021.
  27. ^ "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Monoclonal Antibody Bamlanivimab". U.S. Food and Drug Administration (FDA) (Press release). 16 April 2021. Retrieved 16 April 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  28. ^ a b Swenson, Haylie (December 2020). "2020 Golden Goose Award: A Llama Named Winter". American Association for the Advancement of Science. Retrieved 23 March 2023.
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  30. New York Times
    . 6 May 2020.
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  35. PMID 31371616.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link
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  36. The University of Texas at Austin
    . August 1, 2019. Retrieved 2021-06-02.
  37. PMID 18977045.{{cite journal}}: CS1 maint: multiple names: authors list (link
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  38. PMID 30691364.{{cite journal}}: CS1 maint: multiple names: authors list (link
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  40. PMID 33864736.{{cite journal}}: CS1 maint: multiple names: authors list (link
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  41. ^ "FDA Approves First Respiratory Syncytial Virus (RSV) Vaccine" (Press release). U.S. Food and Drug Administration. May 3, 2023. Retrieved May 3, 2023.
  42. Washington Post
    . May 3, 2023. Retrieved May 3, 2023.
  43. ^ "The race to make vaccines for a dangerous respiratory virus". Nature. 10 Dec 2021. Retrieved 26 April 2022.
  44. Washington Post
    . 10 Oct 2022. Retrieved 11 Oct 2022.
  45. ^ "This UT Scientist Helped Spare Millions From COVID-19. Now He's Unmasking Other Killer Viruses". Texas Monthly. 10 Oct 2022. Retrieved 13 Oct 2022.
  46. ^ "COVID-19 researchers recognized with 2020 Golden Goose Award for scientific contributions" (Press release). American Association for the Advancement of Science. 1 December 2020. Retrieved 23 March 2023.
  47. ^ "William Prusoff Memorial Award". International Society for Antiviral Research. Retrieved 4 June 2020.
  48. ^ "Norman P. Salzman Memorial Award and Symposium in Virology". Foundation for the National Institutes of Health. Retrieved 4 June 2020.
  49. ^ "Hood Foundation Alumni Directory" (PDF). Charles H. Hood Foundation. Retrieved 4 June 2020.
  50. ^ "ACA Award Descriptions". American Crystallographic Association. Retrieved 4 June 2020.
  51. ^ "Viruses Young Investigator in Virology Prize". Viruses. Retrieved 4 June 2020.
  52. ^ "TAMEST 2022 Edith and Peter O'Donnell Awards".
  53. ^ "Creator of breakthrough coronavirus technology to receive inaugural McGuire Prize". EurekAlert. May 2, 2022. Retrieved May 23, 2022.
  54. ^ "Recognizing America's Leading Innovative Scientists, the 2022 Blavatnik National Awards for Young Scientists Names 31 Finalists". Blavatnik Awards for Young Scientists. June 1, 2022. Retrieved February 6, 2023.
  55. ^ "NAS Award in Molecular Biology".
  56. ^ ""The Welch Foundation Announces 2023 Norman Hackerman Award Recipient"". January 23, 2023.
  57. ^ "NAI Welcomes 95 New Emerging Innovators"". February 14, 2023.

External links

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