Optimization of the delivery of heterologous proteins by the Salmonella enterica serovar Typhimurium type III secretion system for vaccine development.
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.
Chen
Li-Mei
LM
Section of Microbial Pathogenesis, School of Medicine, Yale University, New Haven, CT 06536, USA.
Briones
Gabriel
G
Donis
Ruben O
RO
Galán
Jorge E
JE
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006678:HIV / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D021381:Protein Transport; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000276:immunology
D016915:AIDS Vaccines; D001426:Bacterial Proteins; D015683:Gene Products, gag; D012191:Retroviridae Proteins; C103987:SopE protein, Salmonella