Mucosal delivery of a transmission-blocking DNA vaccine encoding Giardia lamblia CWP2 by Salmonella typhimurium bactofection vehicle.
In this study, we investigated the use of Salmonella typhimurium (STM1 strain) as a bactofection vehicle to deliver a transmission-blocking DNA vaccine (TBDV) plasmid to the intestinal immune system. The gene encoding the full length cyst wall protein-2 (CWP2) from Giardia lamblia was subcloned into the pCDNA3 mammalian expression vector and stably introduced into S. typhimurium STM1. Eight-week-old female BALB/c mice were orally immunized every 2 weeks, for a total of three immunizations. Vaccinated and control mice were sacrificed 1 week following the last injection. Administration of the DNA vaccine led to the production of CWP2-specific cellular immune responses characterized by a mixed Th1/Th2 response. Using ELISA, antigen-specific IgA and IgG antibodies were detected in intestinal secretions. Moreover, analysis of sera demonstrated that the DNA immunization also stimulated the production of CWP2-specific IgG antibodies that were mainly of the IgG2a isotype. Finally, challenge infection with live Giardia muris cysts revealed that mice receiving the CWP2-encoding DNA vaccine were able to reduce cyst shedding by approximately 60% compared to control mice. These results demonstrate, for the first time, the development of parasite transmission-blocking immunity at the intestinal level following the administration of a mucosal DNA vaccine delivered by S. typhimurium STM1.
Abdul-Wahid
Aws
A
Institute of Parasitology, McGill University, 21,111 Lakeshore Road, Sainte-Anne-de-Bellevue, Montréal, Québec, Canada H9X-3V9.
Faubert
Gaétan
G
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D005260:Female; D005822:Genetic Vectors; D016829:Giardia lamblia / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005873:Giardiasis / Q000517:prevention & control* / Q000635:transmission; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D019444:Vaccines, DNA