Dr. Galen's research is focused on development of molecular genetics approaches for use in attenuating Salmonella enterica serovars. These efforts involve development of both chromosomal mutagenesis techniques, as well as the engineering of plasmid maintenance technologies for retention of expression vectors within attenuated S. Typhi live vector vaccine strains. Protective antigens of interest, for vaccination of humans using live vectors, originate from the causative agents of malaria, anthrax, botulism, bubonic plague, and SARS.
Galen, J.E. and M.M. Levine. A “flawless” live vector vaccine strain: Can it be engineered? Trends in Microbiology. 2001. 9: 372-376.
Wang, J.Y., M. F. Pasetti, F. R. Noriega, R. J. Anderson, S. S. Wasserman, J.E. Galen, M. B. Sztein, and M.M. Levine. Construction, characterization and immunogenicity of attenuated delta guaBA Salmonella enterica serovar Typhi strain CVD 915. Infect. Immun. 2001. 69: 4734-4741.
Altboum, Z., E.M. Barry, G. Losonsky, J.E. Galen, and M.M. Levine. Attenuated Shigella flexneri 2a delta guaBA strain CVD1204 expressing enterotoxigenic Escherichia coli (ETEC) CS2 and CS3 fimbriae as a live mucosal vaccine against Shigella and ETEC infection. Infect. Immun. 2001; 69: 3150-3158.
Orr, N., J.E. Galen, and M.M. Levine. Novel use of anaerobically induced promoter, dmsA, for controlled expression of Fragment C of tetanus toxin in live attenuated Salmonella enterica serovar Typhi strain CVD 908-htrA. Vaccine. 2001; 19: 1694-1700.
Altboum, Z., M.M. Levine, J.E. Galen, and E.M. Barry. Genetic characterization and immunogenicity of coli surface antigen 4 from enterotoxigenic Escherichia coli when it is expressed in a Shigella live-vector strain. Infect. Immun. 2003; 71: 1352-1360.
Galen, J.E., L. Zhao, M. Chinchilla, J.Y. Wang, M.F. Pasetti, J. Green, and M.M. Levine. Adaptation of the endogenous Salmonella Typhi 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. Immun. 2004. 72: 7096-7106.
Stokes MG, Titball RW, Neeson BN, Galen JE, Walker NJ, Stagg AJ, Jenner DC, Thwaite JE, Nataro JP, Baillie LW, Atkins HS. Oral administration of a Salmonella enterica-based vaccine expressing Bacillus anthracis protective antigen confers protection against aerosolized B. anthracis. Infect. Immun. 2007. 75:1827-34.
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. Immun. 2007. 75:3769-79.
Fang CM, J.Y. Wang, M. Chinchilla , M.M. Levine, W.C. Blackwelder, and J.E. Galen. Use of mchI encoding immunity to the antimicrobial peptide microcin H47 as a plasmid selection marker in attenuated bacterial live vectors. Infect. Immun. 2008. 76: 4422-4430.
Galen JE, M. Chinchilla, M.F. Pasetti, J.Y. Wang, L. Zhao, I. Arciniega-Martinez, D.J. Silverman, and M.M. Levine. 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: 326-35.
Galen, J.E., M.F. Pasetti, S.M. Tennant, P. Olvera-Ruiz, M.B. Sztein, M.M.Levine. Salmonella enterica serovar Typhi Live Vector Vaccines Finally Come of Age. 2009. Immunol. Cell Biol. In press.
Galen J.E., J.Y. Wang, M. Chinchilla, C. Vindurampulle, J.E. Vogel, H. Levy, W.C. Blackwelder, M.F. Pasetti, and M.M. Levine. A new generation of stable, non-antibiotic, low copy number plasmids improve immune responses to foreign antigens in Salmonella enterica serovar Typhi live vectors. Infect. Immun. 2010; 78: 337-47.
Tennant SM, S. Diallo, H. Levy, S. Livio, S.O. Sow, M. Tapia, P.I. Fields, M. Mikoleit, B. Tamboura, K.L. Kotloff, J.P. Nataro, J.E. Galen, and M.M. Levine. Identification by PCR of non-typhoidal Salmonella enterica serovars associated with invasive infections among febrile patients in Mali. PLoS Negl. Trop. Dis. 2010; 4(3):e621.
Ramirez K, Y. Ditamo, J.E. Galen, L.W. Baillie, and M.F. Pasetti. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies. Vaccine. 2010; 28: 6065-75.
Tennant S.M, Y. Zhang, J.E. Galen, C.D. Geddes, and M.M. Levine. Ultra-fast and sensitive detection of non-typhoidal Salmonella using microwave-accelerated metal-enhanced fluorescence ("MAMEF"). PLoS One. 2011. Apr 8;6(4):e18700.
Simon R, S.M. Tennant, J.E. Galen, and M.M. Levine. Mouse models to assess the efficacy of non-typhoidal Salmonella vaccines: Revisiting the role of host innate susceptibility and routes of challenge. Vaccine. 2011. 29: 5094-106.
Tennant S.M, J.Y. Wang, J.E. Galen, R. Simon, M. Pasetti, O. Gat, and M.M. Levine. Engineering and pre-clinical evaluation of attenuated non-typhoidal Salmonella strains serving as live oral vaccines and as reagent strains. Infect. Immun. 2011. 79: 4175-4185.
Simon R, S. Tennant, J.Y. Wang, P. Schmidlein, A. Lees, R. Ernst, M. Pasetti, J. E. Galen, and M.M. Levine. Salmonella enteritidis Core-O Polysaccharide (COPS) conjugated to H:g,m flagellin as a candidate vaccine for protection against invasive infection with Salmonella. Infect. Immun. 2011. 79: 4240-4249.
Gat O, J.E. Galen, S. Tennant, R. Simon, W.C. Blackwelder, D.J. Silverman, M.F. Pasetti, and M.M. Levine. Cell-associated flagella enhance the protection conferred by mucosally-administered attenuated Salmonella Paratyphi A vaccines. PLoS Negl. Trop. Dis. 2011. Nov;5(11):e1373.
Galen J.E., R. Simon, and R.K. Ernst. Salmonella expressing detoxified lipopoly-saccharide is immunogenic and protective both as an attenuated vaccine and for delivery of foreign antigens. Expert Rev Vaccines. 2011; 10: 1679-82.
Mellado-Sanchez G, K. Ramirez, C.B. Drachenberg, J.Diaz-McNair, A.L. Rodriguez, J.E. Galen, J.P. Nataro, and M.F. Pasetti. Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain. Comp. Immunol. Microbiol. Infect. Dis. 2013: 36: 113-28.
Wang J.Y., R. H. Harley, and J.E. Galen. Novel methods for expression of foreign antigens in live vector vaccines. Hum. Vaccin. Immunother. 2013. 9(6). PMID: 23406777. In press.
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