title: A Salmonella typhimurium htrA live vaccine expressing multiple copies of a peptide comprising amino acids 8-23 of herpes simplex virus glycoprotein D as a genetic fusion to tetanus toxin fragment C protects mice from herpes simplex virus infection.
abstract: Multiple tandem copies of an immunogenic epitope comprising amino acids 8-23 of glycoprotein D of herpes simplex virus (HSV) were expressed as C-terminal fusions to tetanus toxin fragment C (TetC) in different Salmonella typhimurium live vaccine strains. Expression of the longer fusions was best in strains harbouring a lesion in htrA, a stress protein gene. SL3261, an aroA strain, did not effectively express the longer fusions. Mice immunised with an S. typhimurium C5 htrA mutant expressing fusions with two or four copies of the peptide made an antibody response to both the peptide and TetC, whereas constructs expressing one copy of the peptide only elicited antibody to TetC. A non-immunogenic octameric fusion underwent rearrangements in vivo resulting in a predominantly monomeric fusion. In contrast, the S. typhimurium SL3261 aroA vaccine expressing the TetC-tetrameric fusion did not elicit antibody to the peptide. Sera from mice immunised with a single dose of the dimer and tetramer fusions in the htrA strain neutralised HSV in vitro, and the mice were protected from HSV infection as measured by a reduction in virus load in the ear pinna. We have previously shown that mice vaccinated with salmonella expressing TetC are protected against tetanus toxin and virulent salmonella challenge. These results suggest that it may be possible to develop a multivalent vaccine against salmonellosis, tetanus and HSV.
authors.affiliation: Department of Microbiology, University of Newcastle, Newcastle upon Tyne, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Chabalgoity
authors.forename: C M
authors.initials: CM
authors.lastname: Khan
authors.forename: A A
authors.initials: AA
authors.lastname: Nash
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000097:blood; D001428:Bacterial Vaccines / Q000235:genetics / Q000627:therapeutic use; D001483:Base Sequence; D005260:Female; D006360:Heat-Shock Proteins; D006561:Herpes Simplex / Q000517:prevention & control*; D007132:Immunoglobulin Isotypes / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D033903:Periplasmic Proteins; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D007132:Immunoglobulin Isotypes; D010446:Peptide Fragments; D033903:Periplasmic Proteins; D011993:Recombinant Fusion Proteins; D013744:Tetanus Toxin; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; C040635:tetanus toxin fragment C; C061682:DegP protease; D012697:Serine Endopeptidases