John R. Mascola Explained

John R. Mascola
Office:Director of the Vaccine Research Center
Deputy2:Julie E. Ledgerwood
Richard A. Koup
Module:
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Fields:Immunology
Virology
Workplaces:National Institutes of Health, National Institute of Allergy and Infectious Diseases, Vaccine Research Center

John R. Mascola is an American physician-scientist, immunologist and infectious disease specialist. He was the director of the Vaccine Research Center (VRC), part of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH).  He also served as a principal advisor to Anthony Fauci, director of NIAID, on vaccines and biomedical research affairs. Mascola is the current Chief Scientific Officer for ModeX Therapeutics.

An internationally recognized expert on vaccine and antibody-based product development,[1] [2] [3] Mascola has led biomedical research efforts targeting a wide breadth of viral pathogens for more than 30 years.

As part of the United States Government COVID-19 Response, Mascola led[4] the Vaccine Development Team (VDT) of Operation Warp Speed facilitating the rapid development, evaluation, and subsequent authorization of effective COVID-19 vaccines.[5]

Education

Mascola graduated from Tufts University[6] in 1981 with a Bachelor of Science degree and earned his medical degree from Georgetown University School of Medicine in 1985.[7] He completed a residency in internal medicine at the Naval Medical Center, San Diego and a fellowship in infectious diseases at the National Naval Medical Center, Bethesda, MD, followed by a fellowship in retroviral diseases at the Walter Reed Army Institute of Research (WRAIR).[8] Mascola completed board-certification in internal medicine and infectious diseases.

Career

Early Biomedical Research

Mascola began his career in biomedical research as a U.S. Navy physician. Upon completion of his medical training, he served as a Staff Research Physician in the Division of Retrovirology, WRAIR from 1993 – 2000. During this time, Mascola advanced multiple studies of HIV immunology and vaccine development. His research demonstrated the importance of neutralizing antibodies in protection against HIV and helped explain the reason that HIV vaccines have not yet been effective.[9] [10]

Leading the Vaccine Research Center

Mascola joined the Vaccine Research Center (VRC) in 2000 as a founding investigator and Principal Deputy Director. In this role, he worked with the Center’s founding director, Gary Nabel, to build a broad research portfolio, including the capacity of the Center to develop and evaluate new vaccines and antibody products.

Mascola was appointed Director of the VRC in 2013[11] and provided leadership to the scientific and clinical research activities of the Center, guiding development of vaccine and antibody-based research programs for diseases of high public health importance. Scientific advances and research include the isolation, characterization and advanced development of antibodies targeting HIV,[12] [13] [14] Ebola[15] [16] [17] [18] and COVID-19, the clinical evaluation of novel vaccine candidates and biologic products targeting respiratory syncytial virus (RSV),[19] [20] influenza,[21] [22] Malaria,[23] [24] and Zika,[25] [26] among others, and strategic collaboration with pharmaceutical and biotech partners advancing VRC products into effective public health interventions.[27]

Novel Vaccine and Antibody-Based Product Research

Mascola’s laboratory[28] research focused on rational design approaches to produce effective vaccine and antibody products to prevent and treat infectious diseases. His laboratory also studies how the immune system generates protective antibody responses against viruses and other infectious pathogens.

In 2010, Dr. Mascola and colleagues discovered an antibody called VRC01 that potently neutralizes the HIV virus. Over the course of a decade, the VRC developed this and more potent antibodies to understand their potential to prevent and treat HIV infection. Investigators at the VRC also discovered an antibody against Ebola, and during the 2018 outbreak in the Democratic Republic of Congo (DRC), this antibody, called mAb114, was shown to dramatically reduce mortality of Ebola virus disease. mAb114 has been developed by Ridgeback Biotherapeutics and licensed for use by the FDA.[29] Other major vaccines and antibodies under development include those for RSV, chikungunya virus[30] and improved vaccines for Influenza.[31]

Response to COVID-19

Mascola and his colleague Barney Graham led the partnerships[32] [33] between the VRC and Moderna to design and develop a successful mRNA vaccine that became mRNA-1273, authorized for use (EUA) in December 2020[34] and with AbCellera and Eli Lilly[35] to isolate a SARS-CoV-2 monoclonal antibodies[36] Ly-CoV555 (bamlanivimab) authorized for use in November 2020 and bebtelovimab authorized for use in February 2022.[37]

Mascola helped establish and lead the Operation Warp Speed Vaccine Development Team (VDT), responsible for coordinating the effort to develop and evaluate the COVID-19 vaccines selected within the US Government portfolio. He also serves as senior member on both NIH and HHS leadership teams that provided recommendations on COVID-19 variants of concern,[38] vaccine boosters and heterologous vaccine platforms.

Professional societies

2002: American Society for Clinical Investigation (ASCI)[39]                                      

2012: Association of American Physicians (AAP)

2014: Fellow, American Academy of Microbiology (AAM)[40]                                      

2017: Elected, National Academy of Medicine (NAM)[41] [42]

Selected awards

2020: Washingtonian Magazine Washingtonians of the Year[43]          

2021: NIH Director’s Award for Outstanding Efforts in the Pursuit of Effective Vaccines and Therapeutics to COVID-19[44]                                            

Notes and References

  1. Web site: 2013-10-18. NIAID Selects New Director of the Vaccine Research Center. 2021-12-09. Global Biodefense. en-US.
  2. Web site: Top vaccine researcher to speak at CTSI Forum. 2021-12-09. www.buffalo.edu. en.
  3. Web site: Inside the quixotic 30-year quest that gave us the Covid-19 treatments, vaccines and could unlock vaccinology's new holy grail. 2021-12-09. Endpoints News. en.
  4. Web site: 2020-07-09. Meet the Researcher Leading NIH's COVID-19 Vaccine Development Efforts. 2021-11-19. NIH Director's Blog. en-US.
  5. News: Rogers. Adam. The NIH's Top Vaccine Maker Wants Warp Speed to Be the New Normal. en-US. Wired. 2021-11-17. 1059-1028.
  6. Web site: e-yearbook.com (tm). Tufts University - Jumbo Yearbook (Medford, MA), Class of 1981, Page 241 of 256 E-Yearbook.com has the largest online yearbook collection of college, university, high school, middle school, junior high school, military, naval cruise books and yearbooks. Search and browse yearbooks online!. 2021-12-04. e-yearbook.com. en-US.
  7. Web site: Medical Alumni Board June 2018 Newsletter. 2021-12-05. myemail.constantcontact.com.
  8. September 2009. Editorial introductions. Current Opinion in HIV and AIDS. en-US. 4. 5. vii. 10.1097/COH.0b013e3283304ea1. 1746-630X.
  9. Mascola. John R.. Montefiori. David C.. 2010. The role of antibodies in HIV vaccines. Annual Review of Immunology. 28. 413–444. 10.1146/annurev-immunol-030409-101256. 1545-3278. 20192810.
  10. Kwong. Peter D.. Mascola. John R.. Nabel. Gary J.. September 2013. Broadly neutralizing antibodies and the search for an HIV-1 vaccine: the end of the beginning. Nature Reviews Immunology. en. 13. 9. 693–701. 10.1038/nri3516. 23969737. 13423553. 1474-1741. free.
  11. Web site: 2015-08-06. NIAID selects new director of the Vaccine Research Center. 2021-11-17. National Institutes of Health (NIH). EN.
  12. Zhou. Tongqing. Georgiev. Ivelin. Wu. Xueling. Yang. Zhi-Yong. Dai. Kaifan. Finzi. Andrés. Kwon. Young Do. Scheid. Johannes. Shi. Wei. Xu. Ling. Yang. Yongping. 2010-08-13. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01. Science. 329. 5993. 811–817. 10.1126/science.1192819. 0036-8075. 2981354. 20616231. 2010Sci...329..811Z.
  13. Wu. Xueling. Zhou. Tongqing. Zhu. Jiang. Zhang. Baoshan. Georgiev. Ivelin. Wang. Charlene. Chen. Xuejun. Longo. Nancy S.. Louder. Mark. McKee. Krisha. O’Dell. Sijy. 2011-09-16. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing. Science. 333. 6049. 1593–1602. 10.1126/science.1207532. 0036-8075. 3516815. 21835983. 2011Sci...333.1593W.
  14. Corey. L.. Gilbert. P.B.. Juraska. M.. Montefiori. D.C.. Morris. L.. Karuna. S.T.. Edupuganti. S.. Mgodi. N.M.. deCamp. A.C.. Rudnicki. E.. Huang. Y.. 2021-03-18. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. The New England Journal of Medicine. 384. 11. 1003–1014. 10.1056/NEJMoa2031738. 0028-4793. 8189692. 33730454.
  15. Misasi. John. Gilman. Morgan S.A.. Kanekiyo. Masaru. Gui. Miao. Cagigi. Alberto. Mulangu. Sabue. Corti. Davide. Ledgerwood. Julie E.. Lanzavecchia. Antonio. Cunningham. James. Muyembe-Tamfun. Jean Jacques. 2016-03-18. Structural and Molecular Basis for Ebola Virus Neutralization by Protective Human Antibodies. Science. 351. 6279. 1343–1346. 10.1126/science.aad6117. 0036-8075. 5241105. 26917592. 2016Sci...351.1343M.
  16. Corti. Davide. Misasi. John. Mulangu. Sabue. Stanley. Daphne A.. Kanekiyo. Masaru. Wollen. Suzanne. Ploquin. Aurélie. Doria-Rose. Nicole A.. Staupe. Ryan P.. Bailey. Michael. Shi. Wei. 2016-03-18. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 351. 6279. 1339–1342. 10.1126/science.aad5224. 26917593. 2016Sci...351.1339C. 206643628. free.
  17. Gaudinski. Martin R.. Coates. Emily E.. Novik. Laura. Widge. Alicia. Houser. Katherine V.. Burch. Eugeania. Holman. LaSonji A.. Gordon. Ingelise J.. Chen. Grace L.. Carter. Cristina. Nason. Martha. 2019-03-02. Safety, Tolerability, Pharmacokinetics, and Immunogenicity of mAb114: A Phase 1 Trial of a Therapeutic Monoclonal Antibody Targeting Ebola Virus Glycoprotein. Lancet. 393. 10174. 889–898. 10.1016/S0140-6736(19)30036-4. 0140-6736. 6436835. 30686586.
  18. Mulangu. Sabue. Dodd. Lori E.. Richard T. Davey. Jr. Mbaya. Olivier Tshiani. Proschan. Michael. Mukadi. Daniel. Manzo. Mariano Lusakibanza. Nzolo. Didier. Oloma. Antoine Tshomba. Ibanda. Augustin. Ali. Rosine. 2019-11-27. A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics. New England Journal of Medicine. 381. 24. 2293–2303. en. 10.1056/NEJMoa1910993. 31774950. 208335835. free. 10680050.
  19. Crank. Michelle C.. Ruckwardt. Tracy J.. Chen. Man. Morabito. Kaitlyn M.. Phung. Emily. Costner. Pamela J.. Holman. LaSonji A.. Hickman. Somia P.. Berkowitz. Nina M.. Gordon. Ingelise J.. Yamshchikov. Galina V.. 2019-08-02. A proof of concept for structure-based vaccine design targeting RSV in humans. Science. 365. 6452. 505–509. 10.1126/science.aav9033. 31371616. 2019Sci...365..505C. 199379888. free.
  20. Ruckwardt. Tracy J.. Morabito. Kaitlyn M.. Phung. Emily. Crank. Michelle C.. Costner. Pamela J.. Holman. LaSonji A.. Chang. Lauren A.. Hickman. Somia P.. Berkowitz. Nina M.. Gordon. Ingelise J.. Yamshchikov. Galina V.. 2021-10-01. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: a phase 1, randomised, open-label, dose-escalation clinical trial. The Lancet Respiratory Medicine. English. 9. 10. 1111–1120. 10.1016/S2213-2600(21)00098-9. 2213-2600. 33864736. 8487912.
  21. Web site: NIH Begins First-in-Human Trial of a Universal Influenza Vaccine Candidate NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  22. Web site: NIH Launches Clinical Trial of Universal Influenza Vaccine Candidate NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  23. Web site: First Human Trial of Monoclonal Antibody to Prevent Malaria Opens NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  24. Web site: Monoclonal Antibody Prevents Malaria in Small NIH Trial NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  25. Web site: NIH Begins Testing Investigational Zika Vaccine in Humans NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  26. Web site: Phase 2 Zika Vaccine Trial Begins in U.S., Central and South America NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  27. Corey. Lawrence. Mascola. John R.. Fauci. Anthony S.. Collins. Francis S.. 2020-05-29. A strategic approach to COVID-19 vaccine R&D. Science. 368. 6494. 948–950. 10.1126/science.abc5312. 32393526. 218600299. free.
  28. Web site: John Mascola, M.D. NIH: National Institute of Allergy and Infectious Diseases. 2021-11-17. www.niaid.nih.gov. en.
  29. Research. Center for Drug Evaluation and. 2021-09-30. FDA approves treatment for ebola virus. FDA. en.
  30. Chen. Grace L.. Coates. Emily E.. Plummer. Sarah H.. Carter. Cristina A.. Berkowitz. Nina. Conan-Cibotti. Michelle. Cox. Josephine H.. Beck. Allison. O’Callahan. Mark. Andrews. Charla. Gordon. Ingelise J.. 2020-04-14. Effect of a Chikungunya Virus–Like Particle Vaccine on Safety and Tolerability Outcomes: A Randomized Clinical Trial. JAMA. 323. 14. 1369–1377. 10.1001/jama.2020.2477. 32286643. 7156994. 0098-7484.
  31. Kanekiyo. Masaru. Joyce. M. Gordon. Gillespie. Rebecca A.. Gallagher. John R.. Andrews. Sarah F.. Yassine. Hadi M.. Wheatley. Adam K.. Fisher. Brian E.. Ambrozak. David R.. Creanga. Adrian. Leung. Kwanyee. March 2019. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses. Nature Immunology. 20. 3. 362–372. 10.1038/s41590-018-0305-x. 1529-2908. 6380945. 30742080.
  32. Web site: NIH Vaccine Research Center Leads the Way to Safe, Effective COVID-19 Vaccines. 2021-11-17. NIH COVID-19 Research. en.
  33. News: LaFraniere. Sharon. Thomas. Katie. Weiland. Noah. Gelles. David. Stolberg. Sheryl Gay. Grady. Denise. 2020-11-21. Politics, Science and the Remarkable Race for a Coronavirus Vaccine. en-US. The New York Times. 2021-11-19. 0362-4331.
  34. Web site: Commissioner. Office of the. 2020-12-21. FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine. 2021-11-17. FDA. en.
  35. Web site: Lilly Begins World's First Study of a Potential COVID-19 Antibody Treatment in Humans Eli Lilly and Company. 2021-11-17. investor.lilly.com. en.
  36. News: Khamsi. Roxanne. May I Borrow Your Covid Immunity?. en-US. Wired. 2021-11-17. 1059-1028.
  37. Company . Eli Lilly and . Lilly's bebtelovimab receives Emergency Use Authorization for the treatment of mild-to-moderate COVID-19 . 2023-06-08 . www.prnewswire.com . en.
  38. Mascola. John R.. Graham. Barney S.. Fauci. Anthony S.. 2021-04-06. SARS-CoV-2 Viral Variants—Tackling a Moving Target. JAMA. 325. 13. 1261–1262. 10.1001/jama.2021.2088. 33571363. 231899701. 0098-7484. free.
  39. Web site: The American Society for Clinical Investigation. 2021-11-19. en-US.
  40. Web site: 79 Fellows elected to the American Academy of Microbiology. 2021-11-19. EurekAlert!. en.
  41. Web site: Member. 2021-11-19. National Academy of Medicine. en-US.
  42. Web site: 2017-10-16. National Academy of Medicine Elects 80 New Members. 2021-11-19. National Academy of Medicine. en-US.
  43. Web site: 2020-12-16. Meet Our 2020 Washingtonians of the Year. 2021-11-19. Washingtonian. en-US.
  44. Web site: 2021 NIAID Awards NIH Director's Awards. 2021-12-12. directorsawards.hr.nih.gov.

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