HSF II, S-359
Education and Training
University of Virginia, B.A., Biochemistry, 1979
University of Maryland School of Medicine, Ph.D., Microbiology & Immunology, 1991
For over 15 years, Dr. Galen has focused on the construction of attenuated bacterial vaccines and their use as live vectors to deliver foreign antigens to the immune system. His work has had broad applications to the development and pre-clinical testing of a variety of live vaccines against both eukaryotic and prokaryotic pathogens, including the etiological agents for malaria, SARS, plague, anthrax, tetanus, enteric fever, and most recently infections caused by Clostridium difficile.
Dr. Galen has been involved in instrumental research on the development of plasmid-based expression systems for delivery of foreign antigens from both prokaryotic and eukaryotic organisms.
He has invented two novel systems:
- Antigen transport system for export of antigens out to the surface of attenuated S. Typhi.
- Plasmid stabilization and selection system that removes the need for plasmid selection using antibiotics and guarantees plasmid retention in vivo after introduction into live vector strains.
Dr. Galen’s work has resulted in multiple patents issued in both the United States and abroad.
Recent efforts have focused on the design and development of novel vaccines and therapeutic treatments against enteric disease caused by Clostridium difficile. On the vaccine side, Dr. Galen has worked on the development of a live oral vaccine designed to elicit toxin neutralizing antibodies against the three known toxins of C. difficile: Toxin A (TcdA), toxin B (TcdB), and binary toxin (CDT). On the therapeutic treatment side, he is collaborating on a unique project to engineer a probiotic strain of yeast called Saccharomyces boulardii to efficiently and stably deliver in situ therapeutically relevant levels of a novel tetravalent neutralizing antibody against CDI enterotoxins TcdA and TcdB, to interrupt recurrent disease.
Attenuated bacterial vaccines, live oral vaccines, malaria, SARS, plague, anthrax, tetanus, enteric fever, enteric disease, plasmid-based expression systems, Clostridium difficile, Acinetobacter baumannii.
Galen JE, Buskirk AD, Tennant SM, Pasetti MF. Live attenuated human salmonella vaccine candidates: tracking the pathogen in natural infection and stimulation of host immunity. EcoSal Plus. In press.
Galen JE, Wang JY, Carrasco JA, Lloyd SA, Mellado-Sanchez G, Diaz-McNair J, Franco O, Buskirk AD, Nataro JP, Pasetti MF. A bivalent typhoid live vector vaccine expressing both chromosome- and plasmid-encoded Yersinia pestis antigens fully protects against murine lethal pulmonary plague infection. Infection and Immunity. 2015; 83(1):161-72.
Galen JE and Curtiss R 3rd. The delicate balance in genetically engineering live vaccines. Vaccine. 2014; 32(35):4376-85.
Wang JY, Harley RH, Galen JE. Novel methods for expression of foreign antigens in live vector vaccines. Hum Vaccin Immunother. 2013; 9(7):1558-64.
Galen JE, Wang JY, Chinchilla M, Vindurampulle C, Vogel JE, Levy H, Blackwelder WC, Pasetti MF, Levine MM. A new generation of stable, non-antibiotic, low copy number plasmids improve immune responses to foreign antigens in Salmonella enterica serovar Typhi live vectors. Infection and Immunity. 2013; 78(1):337-47.
Galen, JE, Pasetti MF, Tennant S, Ruiz-Olvera P, Sztein MB, Levine MM. Salmonella enterica serovar Typhi live vector vaccines finally come of age. 2009; 87(5):400-12.
Galen JE, Chinchilla M, Pasetti MF, Wang JY, Zhao L, Arciniega-Martinez I, Silverman DJ, Levine MM. Mucosal immunization with attenuated Salmonella Typhi expressing anthrax PA83 primes monkeys for accelerated serum antibody responses to parenteral PA83 vaccine. J Infect Dis. 2009; 199(3):326-35.
Chinchilla, M, Pasetti MF, Medina-Moreno S, Wang JY, Gomez-Duarte OG, Stout R, Levine MM, Galen JE. Enhanced immunity to Plasmodium falciparum circumsporozoite protein (PfCSP) by using Salmonella enterica serovar Typhi expressing PfCSP and a PfCSP-encoding DNA vaccine in a heterologous prime-boost strategy. Infect and Immun. 2007; 75(8):3769-79.
Galen, JE, Zhao, L, Chinchilla, M, Wang, JY, Pasetti, MF, Green, J, Levine, MM. Adaptation of the endogenous Salmonella enterica serovarTyphi clyA hemolysin for antigen export enhances the immunogenicity of anthrax protective antigen domain 4 expressed by the attenuated live vector vaccine strain CVD 908-htrA. Infect and Immun. 2004; 72(12):7096-7106.
Tacket, CO, Galen JE, Sztein MB, Losonsky G, Wyant TL, Nataro J, Wasserman SS, Edelman R, Chatfield S, Dougan G, Levine MM. Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C. Clinical Immunology. 2000; 97(2):146-153.
Pickett TE, Pasetti MF, Galen JE, Sztein MB, Levine MM. In vivo characterization of the murine intranasal model for assessing the immunogenicity of attenuated Salmonella enterica serovar Typhi strains as live mucosal vaccines and as live vectors. 2000; 68(1):205-213.
Galen, JE, Gomez-Duarte OG, Losonsky GA, Halpern JL, Lauderbaugh CS, Kaintuck S, Reymann MK, Levine MM. A murine model of intranasal immunization to assess the immunogenicity of attenuated Salmonella typhi live vector vaccines in stimulating serum antibody responses to foreign antigens. Vaccine. 1997; 15(6-7):700-708.
Dr. Galen is interested in the application of novel engineering technologies to the development of live oral vaccines against potentially lethal infections caused by Clostridium difficile and Acinetobacter baumannii.
Myron M. Levine, M.D., D.T.P.H. (PI)
Role: Co-Investigator of Project 2
03/01/14 - 02/28/19
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.
James Galen, Ph.D. (PI)
12/01/12 - 11/30/17
Mucosal live vector vaccine against recurrent Clostridium difficile infections
- Develop a Salmonella-based multivalent oral vaccine against recurrent Clostridium difficile disease which targets both enterotoxins and the binary toxin colonization factor.
Myron M. Levine, M.D., D.T.P.H. (PI)
Role: Co-Investigator and Project Manager
5/14/12 – 11/13/17
Wellcome Trust Strategic Translational Award
Vaccines to prevent invasive non-typhoidal Salmonella infections in infants and young children in sub-Saharan Africa
- Develop and bring to clinical trials two monovalent conjugates (S. Typhimurium and S. Enteritidis) plus a bivalent combination conjugate vaccine against invasive disease caused by Salmonella serovars Typhimuirum and Enteritidis.
United States Patents
Expression plasmids and their use in attenuated S. Typhi live vector vaccines
- 6,413,768: Expression Plasmids, July 2, 2002
- 6,969,513: Plasmid Maintenance System for Antigen Delivery, November 29, 2005
- 6,977,176: December 20, 2005
- 7,125,720: October 24, 2006
- 7,138,112: November 21, 2006
- 7,141,408: November 28, 2006
- 8,076,130: December 31, 2011
Antigen export technology and uses in attenuated S. Typhi live vector vaccines
- 7,056,700: Use of ClyA Hemolysin for Excretion of Proteins, June 6, 2006
- 7,459,161: Methods for Eliciting an Immune Response Using Cytolysin and Hemolysin Fusion Protein, December 2, 2008
Antigen export technology using non-hemolytic versions of ClyA
- 9,051,574: Non-hemolytic ClyA for excretion of proteins, June 9, 2015
Attenuated S. Typhi-based live vector vaccines expressing chromosomally integrated foreign antigens
- 9,446,113: Bacterial live vector vaccines expressing chromosomally-integrated foreign antigens, Sept 20, 2016
Vaccines against non-typhoidal Salmonella disease
- 9,011,871: Broad spectrum vaccine against typhoidal and non-typhoidal Salmonella disease, April 21, 2015
- No. 9,050,283: Broad spectrum vaccine against non-typhoidal Salmonella, June 9, 2015
- Australian Patent No. 200129770: Use of ClyA Hemolysin for Excretion of Proteins, July 19, 2007
- European Patent No. 1412502: Use of ClyA Hemolysin for Excretion of Proteins (validated in France, Germany, Italy, Spain, and the United Kingdom), July 21, 2010
- Indian Patent No. 202579: Use of ClyA Hemolysin for Excretion of Proteins, March 2, 2007
- Japanese Patent No. 3976685: Use of ClyA Hemolysin for Excretion of Proteins, June 29, 2007
- International Patent No. PCT/US2010/56871: Multivalent live vector vaccine against Clostridium difficile-associated disease, November 16, 2010
- European Patent Application No. 10 732 190.3: Broad Spectrum Vaccine Against Non-Typhoidal Salmonella