Immune responses and protection against Bordetella pertussis infection after intranasal immunization of mice with filamentous haemagglutinin in solution or incorporated in biodegradable microparticles.
The intranasal (i.n.) immunization of mice with Bordetella pertussis filamentous haemagglutinin (FHA) either as a solution or incorporated in biodegradable microparticles induced very similar immune responses. Both resulted in strong systemic IgG responses to FHA and good levels of anti-FHA IgG and IgA in the lungs of immunized mice. In comparison, the intraperitoneal (i.p.) immunization of mice with FHA, as a solution, engendered anti-FHA antibody responses which were stronger for serum IgG, similar for lung IgG and lower for lung IgA. The anti-FHA antibody levels, as measured by immunosorbent assay, were shown to correlate with their functional activity in the blocking of B. pertussis adhesion to HeLa tissue-culture cells. All three forms of immunization appeared to stimulate T-cell responses as assessed by in vitro antigen-specific spleen cell proliferation and IL-2 secretion indicative of a Th1 type response, however, cells from i.p. immunized mice only secreted low levels of IL-5. All three methods of FHA immunization provided mice with significant protection against subsequent aerosol challenge with virulent B. pertussis. Mice which had been immunized intra-nasally eliminated the bacteria from their lungs slightly more rapidly than i.p. immunized mice, demonstrating the efficacy of intranasal administration of FHA in solution and in the more practical biodegradable microparticle form.
Cahill
E S
ES
Department of Pharmaceutical Sciences, Nottingham University, UK.
O'Hagan
D T
DT
Illum
L
L
Barnard
A
A
Mills
K H
KH
Redhead
K
K
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D001886:Bordetella pertussis / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006388:Hemagglutinins / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D010567:Pertussis Vaccine; D012996:Solutions; D013154:Spleen / Q000378:metabolism; D014917:Whooping Cough / Q000276:immunology* / Q000517:prevention & control*
D000336:Aerosols; D016207:Cytokines; D006388:Hemagglutinins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010567:Pertussis Vaccine; D012996:Solutions