Vaccination of mice with gonococcal TbpB expressed in vivo from Venezuelan equine encephalitis viral replicon particles.
We investigated the immunogenicity of gonococcal transferrin binding protein B (TbpB) expressed with and without a eukaryotic secretion signal from a nonpropagating Venezuelan equine encephalitis virus replicon particle (VRP) delivery system. TbpB was successfully expressed in baby hamster kidney (BHK) cells, and the presence of the eukaryotic secretion signal not only apparently increased the protein's expression but also allowed for extracellular localization and glycosylation. Mice immunized with VRPs produced significant amounts of serum antibody although less than the amounts produced by mice immunized with recombinant protein. The response of mice immunized with VRPs encoding TbpB was consistently more Th1 biased than the response of mice immunized with recombinant protein alone. Boosting with recombinant protein following immunization with TbpB VRPs resulted in higher specific-antibody levels without altering the Th1/Th2 bias. Most of the immunization groups produced significant specific antibody binding to the intact surface of the homologous Neisseria gonorrhoeae strain. Immunization with TbpB VRPs without a eukaryotic secretion signal generated no measurable specific antibodies on the genital mucosal surface, but inclusion of a eukaryotic secretion signal or boosting with recombinant protein resulted in specific immunoglobulin G (IgG) and IgA in mucosal secretions after TbpB VRP immunization. The TbpB VRP system has potential for an N. gonorrhoeae vaccine.
University of North Carolina at Chapel Hill, Dept. of Medicine, Div. of Infectious Disease Research, 8341 Medical Biomolecular Research Bldg., 103 Mason Farm Road, CB 7031, Chapel Hill, NC 27599, USA. cet@med.unc.edu
Christopher E
CE
Thomas
Weiyan
W
Zhu
Cornelius N
CN
Van Dam
Nancy L
NL
Davis
Robert E
RE
Johnston
P Frederick
PF
Sparling
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics; D005260:Female; D006069:Gonorrhea / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009344:Neisseria gonorrhoeae / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D012093:Replicon / Q000235:genetics / Q000502:physiology*; D033882:Transferrin-Binding Protein B / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014621:Vagina / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D011994:Recombinant Proteins; D033882:Transferrin-Binding Protein B