Levine, Myron | University of Maryland School of Medicine

Academic Title:

Professor

Primary Appointment:

Medicine

Secondary Appointment(s):

Pediatrics, Epidemiology & Public Health, Microbiology and Immunology

Additional Title:

Associate Dean for Global Health, Vaccinology, and Infectious Diseases

Email:

mlevine@som.umaryland.edu

Location:

HSF 1, Room 480

Phone (Primary):

(410) 706-7588

Fax:

(410) 706-6205

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Education and Training

City College of New York, B.S., 1963

Medical College of Virginia, M.D., 1967

London School of Hygiene and Tropical Medicine (with Distinction), D.T.P.H., 1974

Internship, Bronx Municipal Hospital Center, Albert Einstein College of Medicine, Pediatrics, 1967-1968

Residency, Bronx Municipal Hospital Center, Albert Einstein College of Medicine, Pediatrics, 1968-1970

Fellowship, Albert Einstein College of Medicine, Pediatric Infectious Diseases and Immunology, 1970

Fellowship, University of Maryland School of Medicine, Division of Infectious Diseases, 1970-1972

Biosketch

Dr. Levine has worked on infectious disease research, continuously, since 1970. He co-founded the Center for Vaccine Development (CVD) in 1974 and served as Director from inception until 2015. He has spent considerable time in developing countries working on the epidemiology, treatment, and prevention of infectious diseases and applied this field experience to studies of the pathogenesis of such infections and development and testing of vaccines.

For 42 years, Dr. Levine has conducted Phase 1, 2, 3, and 4 clinical trials to evaluate the safety, immunogenicity, and efficacy of a wide array of vaccines; served as a clinician in vaccine testing for both adults and children; designed and supervised domestic and international epidemiologic studies; overseen research activities in the laboratory; and supervised development of diagnostic assays for use in developing countries and subsequent testing in field trials. His laboratory research has focused on the construction and characterization of attenuated strains of Salmonella Typhi, S. Paratyphi A, non-typhoidal Salmonella serovars, and Shigella to serve as live oral vaccines and as live vectors for the expression of foreign antigens. Multiple constructs have progressed from animal models to human trials.

Dr. Levine has designed and supervised large-scale, randomized, controlled field trials that investigated the efficacy of live oral typhoid vaccine Ty21a, which led to its licensure by the US Food and Drug Administration (FDA). Post-licensure work with Haemophilus influenzae type b conjugate vaccine led to early introductions into the routine infant immunization schedule in Chile (1996) and Mali, West Africa (2005). After years of challenge trials and an effective clinical trial, the single-dose oral cholera vaccine, Vaxchora, was approved for licensure by the FDA in 2016.

Research/Clinical Keywords

Salmonella Typhi, S. Paratyphi A, non-typhoidal Salmonella serovars, Shigella, Escherichia coli, Vibrio cholerae O1, Shigella, Haemophilus influenzae, live oral vaccines, vaccine development, conjugate vaccines, clinical trials, pathogenesis, human immune response.

Highlighted Publications

Dr. Levine has 613 peer reviewed papers, 117 book chapters, and is the Senior Editor of the 4^th edition of New Generation Vaccines, a textbook of research vaccinology.

His most recent publications include:

Liu J, Platts-Mills JA, Juma J, Kabir F, Nkeze J, Okoi C, Operario DJ, Uddin J, Ahmed S, Alonso PL, Antonio M, Becker SM, Blackwelder WC, Breiman RF, Faruque AS, Fields B, Gratz J, Haque R, Hossain A, Hossain MJ, Jarju S, Qamar F, Iqbal NT, Kwambana B, Mandomando I, McMurry TL, Ochieng C, Ochieng JB, Ochieng M, Onyango C, Panchalingam S, Kalam A, Aziz F, Qureshi S, Ramamurthy T, Roberts JH, Saha D, Sow SO, Stroup SE, Sur D, Tamboura B, Taniuchi M, Tennant SM, Toema D, Wu Y, Zaidi A, Nataro JP, Kotloff KL, Levine MM , Houpt ER. Use of quantitative molecular diagnostic methods to identify causes of diarrhoea in children: A reanalysis of the GEMS case-control study. Lancet. 2016;388:1291-1301.

Higginson EE, Galen JE, Levine MM, Tennant SM. Microgravity as a biological tool to examine host-pathogen interactions and to guide development of therapeutics and preventatives that target pathogenic bacteria. Pathog Dis. 2016 Sep 13. doi: http://dx.doi.org/10.1093/femspd/ftw095.

Wahid R, Fresnay S, Levine MM, Sztein MB. Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a. Clin Immunol. 2016 Sep 12.

Feasey NA, Hadfield J, Keddy KH, Dallman TJ, Jacobs J, Deng X, Wigley P, Barquist Barquist L, Langridge GC, Feltwell T, Harris SR, Mather AE, Fookes M, Aslett M, Msefula C, Kariuki S, Maclennan CA, Onsare RS, Weill FX, Le Hello S, Smith AM, McClelland M, Desai P, Parry CM, Cheesbrough J, French N, Campos J, Chabalgoity JA, Betancor L, Hopkins KL, Nair S, Humphrey TJ, Lunguya O, Cogan TA, Tapia MD, Sow SO, Tennant SM, Bornstein K, Levine MM, Lacharme-Lora L, Everett DB, Kingsley RA, Parkhill J, Heyderman RS, Dougan G, Gordon MA, Thomson NR. Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low -income settings. Nat Genet. 2016 Aug 22;48:1211-1217. doi: 10.1038/ng.3644.

Darton TC, Jones C, Blohmke CJ, Waddington CS, Zhou L, Peters A, Haworth K, Sie R, Green CA, Jeppesen CA, Moore M, Thompson BAV, John T, Kingsley RA, Yu LM, Voysey M, Hindle Z, Lockhart S, Sztein MB, Dougan G, Angus B, Levine MM, Pollard AJ. Using a Human Challenge Model of Infection to Measure Vaccine Efficacy: A Randomised, Controlled Trial Comparing the Typhoid Vaccines M01ZH09 with Placebo and Ty21a. PLoS Negl Trop Dis. 2016 Aug 17;10(8). doi: 10.1371/journal.pntd.0004926.

Additional Publication Citations

Qamar FN, Nisar MI, Quadri F, Shakoor S, Sow SO, Nasrin D, Blackwelder WC, Wu Y, Farag T, Panchalingham S, Sur D, Qureshi S, Faruque AS, Saha D, Alonso PL, Breiman RF, Bassat Q, Tamboura B, Ramamurthy T, Kanungo S, Ahmed S, Hossain A, Das SK, Antonio M, Hossain MJ, Mandomando I, Mintz ED, Tennant SM, Kotloff KL, Levine MM, Zaidi AK. Aeromonas-associated diarrhea in children under 5 years: The GEMS experience. Am J Trop Med Hyg. 2016 Aug 15. pii: 16-0321.

Omore R, Tate JE, O'Reilly CE, Ayers T, Williamson J, Moke F, Schilling KA, Awuor AO, Jaron P, Ochieng JB, Oundo J, Parashar UD, Parsons MB, Bopp CC, Nasrin D, Farag TH, Kotloff KL, Nataro JP, Panchalingam S, Levine MM, Laserson KF, Nuorti JP, Mintz ED, Breiman RF. Epidemiology, seasonality and factors associated with Rotavirus infection among children with moderate-to-severe diarrhea in rural western Kenya, 2008-2012: The Global Enteric Multicenter Study (GEMS). PLoS One. 2016 Aug 5.

Toapanta FR, Bernal PJ, Fresnay S, Magder LS, Darton TC, Jones C, Waddington CS, Blohmke CJ, Angus B, Levine MM, Pollard AJ, Sztein MB. Oral challenge with wild-type Salmonella Typhi induces distinct changes in B cell subsets in individuals who develop typhoid disease. PLoS Negl Trop Dis. 2016 Jun 14;10(6):e000476. doi: 10.1371/journal.pntd.0004766.

Sow SO, Muhsen K, Nasrin D, Blackwelder WC, Wu Y, Farag TH, Panchalingam S, Sur D, Zaidi AK, Faruque AS, Saha D, Adegbola R, Alonso PL, Breiman RF, Bassat Q, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ahmed S, Qureshi S, Quadri F, Hossain A, Das SK, Antonio M, Hossain MJ, Mandomando I, Nhampossa T, Acácio S, Omore R, Oundo JO, Ochieng JB, Mintz ED, O'Reilly CE, Berkeley LY, Livio S, Tennant SM, Sommerfelt H, Nataro JP, Ziv-Baran T, Robins-Browne RM, Mishcherkin V, Zhang J, Liu J, Houpt ER, Kotloff KL, Levine MM. The burden of Cryptosporidium diarrheal disease among children < 24 months of age in moderate/high mortality regions of sub-Saharan Africa and South Asia, utilizing data from the Global Enteric Multicenter Study (GEMS). PLoS Negl Trop Dis. 2016 May 24;10(5):e0004729. doi: 10.1371/journal.pntd.0004729.

Blohmke CJ, Darton TC, Jones C, Suarez NM, Waddington CS, Angus B, Zhou L, Hill J, Clare S, Kane L, Mukhopadhyay S, Schreiber F, Duque-Correa MA, Wright JC, Roumeliotis TI, Yu L, Choudhary JS, Mejias A, Ramilo O, Shanyinde M, Sztein MB, Kingsley RA, Lockhart S, Levine MM, Lynn DJ, Dougan G, Pollard AJ. Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever. J Exp Med. 2016 May 30;213(6):1061-77. doi: 10.1084/jem.20151025.

Levine MM and Pasetti MF. Serologic monitoring is key to sustain progress of the maternal and neonatal tetanus elimination initiative. Clin Vaccine Immunol. 2016 Jul 5;23(7):532-4. doi: 10.1128/CVI.00259-16.

Tapia MD, Sow S, Tamboura B, Teguete I, Pasetti MF, Kodio M, Onwuchekwa U, Tennant SM, Blackwelder WC, Coulibaly F, Traore A, Keita AM, Haidara FC, Diallo F, Doumbia M, Sanogo D, DeMatt, E, Schluterman NH, Buchwald A, Kotloff KL, Chen WH, Orenstein EW, Orenstein LAV, Villanueva J, Bresee J, Treanor JJ, Levine MM. Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial. Lancet Infect Dis. 2016; pii: S1473-3099(16)30054-8. doi: 10.1016/S1473-3099(16)30054-8.

Baker KK, O'Reilly CE, Levine MM,, Kotloff KL, Nataro JP, Ayers TL, Farag TH, Nasrin D, Blackwelder WC, Wu Y, Alonso PL, Breiman RF, Omore R, Faruque AS, Das SK, Ahmed S, Saha D, Sow SO, Sur D, Zaidi AK, Quadri F, Mintz ED. Sanitation and hygiene-specific risk factors for moderate-to-severe diarrhea in young children in the Global Enteric Multicenter Study, 2007-2011: Case-control study. PLoS Medicine. 2016 May 3;13(5):e1002010. doi: 10.1371/journal.pmed.1002010.

Clinical Specialty Details

Dr. Levine has conducted Phase 1, 2, 3 and 4 clinical trials to evaluate the safety, immunogenicity, and efficacy of an array of vaccines in both pediatric and adult populations and has pioneered clinical trials in developing countries, including vaccines developed at the CVD. He has developed experimental challenge models in community volunteers to study the pathogenesis and human immune response to pathogens to guide vaccine development and assess preliminary efficacy of vaccines against diarrheagenic Escherichia coli, Vibrio cholerae O1, Shigella, and other pathogens.

Awards and Affiliations

1995: Member, Institute of Medicine (now the National Academy of Medicine), National Academy of Sciences

1998: Albert B. Sabin Gold Medal Award of the Albert B. Sabin Vaccine Institute for contributions in the field of vaccinology

2012: Maurice Hilleman/Merck Award of the American Society for Microbiology for vaccine discovery, vaccine development, and control of vaccine-preventable diseases

2013: Donald Mackay Medal of the American Society of Tropical Medicine and Hygiene in recognition of outstanding research on tropical health

2014: Dean’s Distinguished Gold Medal, University of Maryland School of Medicine

2015: American College of Physicians Award for Outstanding Work in Science as Related to Medicine

2017: National Foundation for Infectious Diseases (NFID) Maxwell Finland Award for Scientific Achievement

Grants and Contracts

Myron M. Levine, M.D., D.T.P.H. (PI)
5U19AI109776-02
03/01/14-02/28/19
National Institutes of Health (NIH)
Immunoprophylactic strategies to control emerging enteric infections

Five projects in this Enteric Center for Excellence in Translation Research (Enteric CETR) grant to develop products to prevent enteric disease caused by: 1] the typhoidal Salmonella serovars; 2] Clostridium difficile; 3] Shigella and pathogenic E. coli; 4] non-typhoidal group C Salmonella serovars; and 5] Cryptosporidium.

Myron M. Levine, M.D., D.T.P.H. (PI)
7/2013-5/2018
NIH
Fellowship training program in vaccinology (T32)

Myron M. Levine, M.D., D.T.P.H. (PI)
4/2012-10/2016
Wellcome Trust, UK
Parenteral conjugate vaccines to prevent invasive non-typhoidal Salmonella infections in infants and young children in sub-Saharan Africa

Myron M. Levine, M.D., D.T.P.H. (PI)
11/21/14-9/30/2016
Leidos
Accelerated clinical evaluation of monovalent and nivalent vectored Ebola vaccines

Myron M. Levine, M.D., D.T.P.H. (PI)
11/2012-8/2016
Bill & Melinda Gates Foundation
A point-of-care rapid assessment tool to detect protective levels of vaccine-related antibodies in oral (crevicular) fluid of infants, toddlers, and older subjects

Patents

United States Patents

4,935,364, 5,135,862, and 5,470,729: Method of isolating restriction fragment deletions in Vibrio cholerae and products thereof, 1990, 1992, and 1995.

Inventors: Myron M. Levine and James B. Kaper

5,399,494 and 5,628,994: Vibrio cholerae strain CVD103HgR, method of naking same, and vaccines derived therefrom, 1997.

Inventors: Myron M. Levine and James B. Kaper

5,882,653: Vibrio cholerae O1 (CVD111) and non‑O1 (CVD112 and CVD112RM) serogroup vaccine strains, methods of making same and products thereof, YEAR.

Inventors: Myron M. Levine and James B. Kaper

5,189,151: Highly specific DNA probe for enteroaggregative Escherichia coli, 1993.

Inventors: Bernadette Baudry and Myron M. Levine

5,468,639: Isolated DNA molecule encoding ShET2 of Shigella flexneri 2a, 1993.

Inventors: Alessio Fasano, Myron M. Levine, Fernando Noriega, James P. Nataro

5,589,380: Isolated DNA molecule encoding ShET1 of Shigella flexneri 2a, 1996.

Inventors: Alessio Fasano, Myron M. Levine, Fernando Noriega, James P. Nataro

5,783,196: Gua mutants of Shigella spp. and vaccines containing the same, 1998.

Inventors: Fernando Noriega and Myron M. Levine

6,190,669: Attenuated mutants of Salmonella which constitutively express the Vi antigen, 2001.

Inventors: Myron M. Levine, Fernando Noriega, Marcelo B. Sztein

6,902,736 B2: Isolation and characterization of the CSA operon (ETEC-CS4 pili) and methods of using same, 2005.

Inventors: Zeev Altboum, Myron M. Levine, Eileen M. Barry

8,475,810: Attenuated Salmonella enterica serovar paratyphi and uses thereof, 2013.

Inventors: Eileen M. Barry, Myron M. Levine, and Christofer Vindurampulle

8,137,930: Attenuated Salmonella enterica Paratyphi A and uses thereof, 2012.

Christofer Vindurampulle, Myron M. Levine, Eileen M. Barry, and James E. Galen

9,050,283: Broad spectrum vaccine against non-typhoidal Salmonella, 2016.

Inventors: Myron M. Levine, Raphael Simon, James Galen, and Sharon Tennant

9,011,871: Broad spectrum vaccine against typhoidal and non-typhoidal Salmonella disease, 2015.

Inventors: Myron M. Levine, James Galen, Raphael Simon, and Sharon Tennant

Provisional patent application number 62/146,545: Compositions and methods for producing bacterial conjugate vaccines, filded April 13, 2016.

Inventors: Raphael Simon, Myron M. Levine, and Sharon M. Tennant

International Patents

South African patent No. 91/4286: Method of isolating restriction fragment deletions in Vibrio cholerae and products thereof, 1992.

Inventors: Myron M. Levine and James B. Kaper

European Patent Office patent No. 0119031: Virulent Vibrio cholerae and methods for its production.

Inventors: Myron M. Levine and James B. Kaper

Foreign patent Nos. 1076566, 754795, 2,328,056: Attenuated mutants of Salmonella which constitutively express the Vi antigen.

Inventors: Myron M. Levine, Fernando Noriega, Marcelo B. Sztein

Foreign patent Nos. 200125543, 1280912, 2002/9042,246230, 522272: Isolation and characterization of the CSA operon (ETEC-CS4 pili) and methods of using same.

Inventors: Zeev Altboum, Myron M. Levine, Eileen M. Barry

Foreign patent No. 1941024: Attenuated salmonella enterica serovar paratyphi a and uses thereof.

Inventors: Eileen M. Barry, Myron M. Levine, and Christofer Vindurampulle

Myron M. Levine, MD, DTPH

Simon and Bessie Grollman Distinguished Professor