Evaluation of Venezuelan Equine Encephalitis (VEE) replicon-based Outer surface protein A (OspA) vaccines in a tick challenge mouse model of Lyme disease.
Venezuelan Equine Encephalitis (VEE) virus replicon particles (VRPs) encoding Borrelia burgdorferi Outer surface protein A (OspA) were evaluated for their ability to induce an immune response and provide protection from tick-borne spirochetes. VRPs expressing ospA that accumulated intracellularly (VRP OspA) or that was secreted from host cells (VRP tPA-OspA) were tested. Both VRP OspA and VRP tPA-OspA expressed ospA in immunized mice. Mice vaccinated with VRPs expressing secreted OspA produced significant amounts of anti-OspA antibodies, whereas VRPs expressing intracellular OspA were less immunogenic. The VRP method of delivery induced a Th1 type immune response unlike the recombinant OspA protein in Freund's adjuvant, which induced a mixed (Th1 and Th2) immune response. The VRP tPA-OspA construct induced an immune response that reduced the bacterial load in feeding Ixodes scapularis and blocked transmission to the host. These results indicate that VRPs are capable of providing protection against tick-borne B. burgdorferi, and potentially can be used for developing improved vaccines against Lyme disease.
Gipson
Clay L
CL
Department of Microbiology and Immunology, University of North Carolina, CB# 7290, Chapel Hill, NC 27599, USA.
Davis
Nancy L
NL
Johnston
Robert E
RE
de Silva
Aravinda M
AM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines; D002478:Cells, Cultured; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000096:biosynthesis; D007150:Immunohistochemistry; D008074:Lipoproteins; D008193:Lyme Disease / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D022123:Lyme Disease Vaccines / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D012093:Replicon / Q000235:genetics / Q000276:immunology*; D013987:Ticks / Q000382:microbiology*
D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D008074:Lipoproteins; D022123:Lyme Disease Vaccines; C072045:OspA protein; D012367:RNA, Viral