Dr. Levine has been Director of the Center for Vaccine Development since its inception in 1974 and has created therein an academic vaccinology environment that is rich in intellectual ferment and stimulation. Mike Levine is clinically trained in pediatrics and pediatric infectious diseases and is also trained in tropical public health and epidemiology. Post-graduate laboratory training was in microbiology and immunology of bacterial infections (mentored by Dr. John B. Robbins). He served as a World Health Organization consultant to the Smallpox Eradication Program in Bangladesh in 1975 where he was District Coordinator for Rajshahi District. He was a member of the first Working Group of the Global Alliance for Vaccine and Immunization (now called the GAVI Alliance) (2000-2002) and was Co-Chair of its Task Force on Research and Development.
Dr. Levine has published over 460 peer reviewed journal articles, is an inventor or co-inventor on many issued patents and is Senior Editor of New Generation Vaccines, a textbook of research vaccinology. He was elected to the Institute of Medicine of the National Academy of Science, the Association of American Physicians, the American Society of Clinical Investigation and the Interurban Clinical Club. He is the recipient of the Albert B. Sabin Gold Medal Award for lifetime achievement in the area of vaccine development and implementation and has also received the Merck-Hilleman Award, the American Society for Microbiology’s premier award for major contributions to pathogenesis, vaccine discovery, vaccine development, and control of vaccine preventable diseases.
Dr. Levine’s research has focused on infectious diseases that afflict infants, children and adults in developing countries, including cholera, typhoid and paratyphoid fevers, Shigella dysentery, Escherichia coli diarrhea, and invasive infections (e.g., sepsis, meningitis) caused by Haemophilus influenzae type b (Hib), Streptococcus pneumoniae and non-typhoidal Salmonella (NTS), among other pathogens. He has been involved in the gamut of vaccine development research ranging from field studies to quantify disease burden, basic laboratory efforts to study pathogenesis of bacterial enteropathogens and to engineer candidate vaccines, clinical trials to evaluate the safety and immunogenicity of candidate vaccines, large-scale controlled field trials to assess vaccine efficacy and measurement of the public health impact following widespread introduction of vaccines. Thus, his extensive contributions range from basic research to public health implementation.
A fundamental strategy promulgated by Dr. Levine and colleagues has been to delete virulence genes from bacterial enteropathogens such as Salmonella and Shigella to achieve attenuation while maintaining immunogenicity. Clinically well-tolerated, immunogenic attenuated live oral vaccine candidates to prevent typhoid fever (CVD 909), paratyphoid A fever (CVD 1902) and shigellosis (CVD 1208S) have resulted. Pursuing a versatile vaccinology approach, he and colleagues pioneered the engineering of these attenuated strains to serve as "live vector vaccines" to deliver to the host immune system expressed antigens of unrelated pathogens (e.g., Plasmodium falciparum CSP, fragment C of tetanus toxin, Bacillus anthracis protective antigen, various E. coli antigens). More recently he has pursued the development of conjugate vaccines to prevent invasive non-typhoidal Salmonella (mainly S. Typhimurium and S. Enteritidis) disease using flagellin subunits from the homologous serovars as the carrier protein and constructing attenuated “reagent” strains that hyper-express flagellin and release it into the medium without polymerization.
Professor Levine is also one of the world’s most experienced clinical vaccinologists and over the decades has evaluated a panoply of bacterial, viral, and malaria vaccines in clinical trials in pediatric and adult populations in many countries. He has designed and supervised multiple large-scale, randomized, controlled field trials to assess vaccine efficacy pre-licensure. These include four efficacy trials of different formulations and schedules of Ty21a live oral typhoid vaccine that cumulatively enrolled > 465,000 Chilean schoolchildren, followed for 3-7 years. Results of these trials led the FDA to license Ty21a in 1989. Levine designed a post-licensure evaluation of Hib conjugate vaccine in Chile that demonstrated 90% effectiveness under routine public health conditions. Thereupon, the Chilean government in the mid-1990s introduced the vaccine into its EPI, becoming the second non-industrialized country to do so. For more than 3 decades he served as the Principal Investigator of Vaccine Treatment and Evaluation Unit (VTEU) and similar N01 NIH research contracts that maintained the infrastructure for early vaccine clinical trials.
At CVD-Mali, the CVD field unit in Mali, West Africa, Levine established a clinical microbiology laboratory in the public hospital that admits acutely ill children to measure the burden of invasive bacterial infections. Systematic blood culture surveillance of all children admitted to hospital with fever or suspected invasive bacterial syndromes (e.g., meningitis) revealed that Haemophilus influenzae type b (Hib), S. pneumoniae and NTS accounted for the vast majority of hospitalizations for invasive bacterial disease among children. Levine worked with Dr. Samba Sow (Director General of CVD-Mali) and Ministry of Health counterparts to introduce Hib vaccine into the Malian Expanded Programme on Immunization (EPI) in 2005. He obtained a Bill & Melinda Gates Foundation grant to measure the impact of this intervention and showed that within 3 years following vaccine introduction, the incidence of hospitalizations due to culture-confirmed invasive Hib disease fell by 88%. In parallel, serosurveys of randomly selected infants 6-7 months of age revealed that prior to the introduction of Hib vaccine only 0.5% of infants had high titers (> 1.0 mcg/ml) of protective serum antibodies against the capsular polysaccharide of Hib, whereas 30 months after introduction routine infant immunization with Hib conjugate > 80% of infants had high titers.Dr. Levine coordinated the “Global Enteric Multicenter Study” (GEMS) supported by the Bill & Melinda Gates Foundation that has measured the burden of severe pediatric diarrheal disease in 7 countries in sub-Saharan Africa and South Asia, utilizing molecular diagnostic techniques to identify the etiologic agents and assess antigenic diversity. GEMS is establishing the need for particular vaccines and therapeutics, identifying target populations for immunization and providing the baseline against which the public health impact of enteric vaccines can be measured after programmatic deployment.
He successfully competed for a grant that supports a large-scale effectiveness trial to determine whether immunization of 3rd trimester pregnant women in Mali with influenza vaccine will protect their infants < 6 months of age, as well as themselves, against laboratory-confirmed influenza illness.
Some recent publications
- Tennant SM, Wang JY, Galen JE, Simon R, Pasetti MF, Gat O, Levine MM. Engineering and pre-clinical evaluation of attenuated non-typhoidal Salmonella strains serving as live oral vaccines and as reagent strains. Infect.Immun. 2011; 79:4175-85.
- Simon R, Tennant SM, Wang JY, Schmidlein PJ, Lees A, Ernst RK, Pasetti MF, Galen JE, Levine MM. Salmonella Enteritidis Core-O Polysaccharide (COPS) conjugated to H:g,m flagellin as a candidate vaccine for protection against invasive infection with Salmonella Enteritidis. Infect.Immun. 2011; 79:4240-9.
- Gat O, Galen JE, Tennant S, Simon R, Blackwelder WC, Silverman DJ, Pasetti MF, Levine MM. Cell-associated flagella enhance the protection conferred by mucosally-administered attenuated Salmonella Paratyphi A vaccines. PLoS.Negl.Trop.Dis. 2011; 5:e1373.
- Levine, M. M. "Ideal" vaccines for resource poor settings. Vaccine. 2012; 29 Suppl 4:D116-25. doi: 10.1016/j.vaccine.2011.11.090.
- Levine MM, Robins-Browne RM. Factors that explain excretion of enteric pathogens by persons without diarrhea. Clin.Infect.Dis. 2012; 55 Suppl 4:S303-11. doi: 10.1093/cid/cis789.:S303-S311.
Links of Interest:Center for Vaccine Development
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