Department of Microbiology

Sylvie Alonso


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Sylvie Alonso PhD

Assistant Professor, Immunology Programme
Department of Microbiology, NUS CeLs #03-05 28 Medical Drive Singapore 117456

Tel: +65 6516 3541
Email: micas@nus.edu.sg

Host-pathogen Interactions - Development of live bacterial vaccines

Our research interests involve exploring host-pathogen interactions in order to better understand the role of bacterial virulence factors in pathogenicity and in the induction of immune responses in the host. In particular, we currently focus on the mechanisms involved in the persistence of Mycobacterium tuberculosis and the implications for drug susceptibility and vaccine efficacy. We are also investigating the virulence mechanisms of Bordetella pertussis, the agent of whooping cough.

Increased knowledge in host-bacteria relationships may also be very helpful to develop vaccination strategies involving bacteria as delivery systems. Live recombinant bacteria represent an attractive means to induce both mucosal and systemic immune responses against heterologous antigens. The strategy for the expression of the passenger molecule, the invasiveness, the immunogenicity, as well as the safety of the bacterial vector have to be considered altogether.

We develop mucosal (oral and nasal) vaccines against various pathogens including Dengue virus, Enterovirus 71 and influenza virus using live recombinant bacteria as delivery system. The highly attenuated strain of Bordetella pertussis as well as the food-grade Lactococcus lactis bacterium are used as vehicles for the delivery of the vaccine candidates.

Foo, GWD, MacAry, PA, Poh, CL and Alonso S (2008) Identification of human CD4+ T cell epitopes on the VP1 capsid protein of Enterovirus 71. Viral. Immunol. In Press. Co-corresponding Authors

Sim, ACN, Lin, W, Tan, GKX, Sim, MST, Chow, VTK and Alonso S (2008) Induction of neutralizing antibodies against dengue virus type 2 upon mucosal administration of a recombinant Lactococcus lactis strain expressing envelope domain III antigen. Infect. Immun. Vaccine Ahead of print. Equal contribution.

Ho SY, Chua, Foo SQ, GWD, Locht C, Chow VTC, Poh CL and Alonso S (2007) The highly attenuated Bordetella pertussis BPZE1 strain as a potential live vehicle for the delivery of heterologous vaccine candidates. Infect. Immun. 76:111-119

Foo GWD, Alonso S, Chow VTC, and Poh CL (2007) Passive protection against lethal enterovirus 71 infection in newborn mice by neutralizing antibodies elicited by a synthetic peptide. Microbes. Infect. 9:1299-1306

Alonso S, Pethe K, Russell DG, and Purdy GE (2007) Lysosomal killing of Mycobacterium by ubiquitin-derived peptides is enhanced by autophagy. Proc. Natl. Acad. Sci. USA. 104:6031-6036

Alonso S, Willery, E, Renauld-Mongenie G and Locht C (2005) Production of nontypeable Haemophilus influenzae HtrA by recombinant Bordetella pertussis with the use of filamentous hemagglutinin as a carrier. Infect. Immun. 73:4295-4301

Pethe K, Temmerman S, Parra M, Alonso S , Rouanet C, Picket T, Drowalt A, Debrie AS, Delogu G, Menozzi FD, Sergheraert C, Brennan MJ, Mascart F, and Locht C (2004) Methylation-dependent T cell and protective immunity to Mycobacterium tuberculosis heparin-binding haemagglutinin. Nat. Med. 10:935-41

Alonso S, Coutte L, Reveneau N, Willery E, Quatannens B, Locht C, and F Jacob-Dubuisson (2003) Role of adhesin release for mucosal colonization by a bacterial pathogen. J. Exp. Med. 197:735-742

Alonso S, Pethe K, Mielcarek N, Raze D, and Locht C (2001) Role of ADP-ribosyltransferase activity of pertussis toxin in toxin-adhesin redundancy with filamentous hemagglutinin during Bordetella pertussis infection. Infect. Immun. 69:6038-6043

Pethe, K, Alonso S, Biet, F, Brennan, MJ, Locht, C, and FD Menozzi (2001) The heparin-binding haemagglutinin of M. tuberculosis is required for extrapulmonary dissemination. Nat. 412:190-194

Current Projects:
	Persistence of Mycobacterium tuberculosis within the phagolysosomes of activated macrophages
	Using Bordetella pertussis to deliver EV71 antigen vaccine candidates
	Using Bordetella pertussis to deliver influenza A virus antigen vaccine candidates
	Lactococcus lactis as delivery system for Dengue vaccine candidates

Lab Members:
	Lin Wenwei Research Assistant MICLWW@nus.edu.sg
	Angelyn Seet Research Assistant
	Teo Lili Lab Officer MICTLL@nus.edu.sg
	Goh Ting Kiam Lab Officer MICGOHTK@nus.edu.sg
	LiRui PhD student g0500035@nus.edu.sg
	Lim Annabelle Postgraduate Student g0700053@nus.edu.sg
	Tan Grace Postgraduate Student u0306086@alumni.nus.edu.sg
	Khong Wei Xin Undergraduate Student u0402957@nus.edu.sg
	Cheng XuanHao Undergraduate Student u0402168@nus.edu.sg
	Neo Yi Lin Undergraduate Student u0402552@nus.edu.sg
	Ow Stephanie Undergraduate Student u0402634@nus.edu.sg
	Loh Kelvin Medical Student med10093@nus.edu.sg

Lab Phone Contacts:
	+65 6516 3673 (Study Area)
	+65 6516 7578 (Lab Area)