Naked DNA when co-administered intranasally with heat-labile enterotoxin of Escherichia coli primes effectively for systemic B- and T-cell responses to the encoded antigen

• Published in: Immunology letters 2000-11, Vol.74 (3), p.215-220
• Main Authors: Kanellos, Theophanis S., Byarugaba, Denis K., Russell, Peter H., Howard, Colin R., Partidos, Charalambos D.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Animals; Antibodies, Bacterial - biosynthesis; Antibodies, Bacterial - immunology; Antibody Affinity; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; B-Lymphocytes - immunology; Bacterial Toxins - administration & dosage; Bacterial Toxins - pharmacology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - immunology; beta-Galactosidase - genetics; beta-Galactosidase - immunology; DNA, Bacterial - administration & dosage; DNA, Bacterial - genetics; Enterotoxins - administration & dosage; Enterotoxins - pharmacology; Escherichia coli; Escherichia coli Proteins; Female; Immunity, Cellular; Immunization - methods; Immunization, Secondary; Immunoglobulin G - biosynthesis; Immunoglobulin G - immunology; Injections, Intraperitoneal; Intranasal immunisation; Lac Operon; LacZ protein; Mice; Mice, Inbred BALB C; Mucosal adjuvants; Plasmid DNA; Plasmids - genetics; T-Lymphocytes - immunology; Th2 Cells - immunology; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/S0165-2478(00)00257-1

In this study a novel prime-boost immunisation strategy was evaluated. Priming of BALB/c mice by the intranasal route with plasmid DNA encoding β-galactosidase (LacZ) with or without heat-labile enterotoxin (LT) of Escherichia coli as a mucosal adjuvant, resulted in the induction of weak serum antibody and proliferative T-cell responses. However, following an intraperitoneal booster injection with the β-galactosidase protein (β-gal), strong antibody and proliferative T-cell responses were induced in all the mice. These responses were highest in mice primed intranasally with a mixture of LacZ+LT as compared to those mice primed with DNA (LacZ) or protein (β-gal) alone. Moreover, LacZ+LT primed mice produced high avidity antibodies and the subclasses of serum antibodies were IgG1 and IgG2a, suggesting a mixed Th1/Th2-type response. Priming of mice with either protein (β-gal) or DNA (LacZ) alone, produced predominantly IgG1 antibodies, suggesting a Th2-type response. These findings suggest that the use of a heterologous DNA-prime, protein-boost immunisation scheme combining different routes of administration, might be an advantageous strategy for the induction of accelerated immune responses.