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Infection and Immunity, October 2006, p. 5826-5833, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00375-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Optimization of the Delivery of Heterologous Proteins by the Salmonella enterica Serovar Typhimurium Type III Secretion System for Vaccine Development

Li-Mei Chen ,^1,, Gabriel Briones,^1, Ruben O. Donis,² and Jorge E. Galán^1*

Section of Microbial Pathogenesis, School of Medicine, Yale University, New Haven, Connecticut 06536,¹ Influenza Branch, Centers for Disease Control and Prevention, Atlanta, Georgia 30333²

Received 7 March 2006/ Returned for modification 25 April 2006/ Accepted 17 July 2006

Type III protein secretion systems, which are organelles with the capacity to deliver bacterial proteins into host cells, have been adapted to deliver heterologous antigens for vaccine development. A limitation of these antigen delivery systems is that some proteins are not amenable to secretion through this pathway. We show here that proteins from the simian and human immunodeficiency viruses that are not permissive for secretion through a Salmonella enterica serovar Typhimurium type III secretion system can be modified to travel this secretion pathway by introduction of discrete mutations. Proteins optimized for secretion were presented more efficiently via the major histocompatibility complex class I pathway and were able to induce a better immune response.

Editor: J. B. Bliska

L.-M.C. and G.B. contributed equally to this work.

Present address: Influenza Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333.

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