Strong mucosal and systemic immunities induced by nasal immunization with anthrax protective antigen protein incorporated in liposome-protamine-DNA particles.
OBJECTIVE
The very lengthy and complicated dosing schedule of the current anthrax vaccine adsorbed, which was licensed in the USA for the prevention of cutaneous anthrax infection, calls for the development of an efficacious and easily administrable vaccine to prevent against the most lethal form of anthrax infection, the inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein carried by liposome-protamine-DNA (LPD) particles.


METHODS
PA was incorporated in LPD particles and nasally dosed to mice. The resulting PA-specific immune response and lethal toxin neutralization activity were measured.


RESULTS
Mice nasally immunized with PA incorporated into LPD particles developed both systemic and mucosal anti-PA responses. The anti-PA immunities induced included the production of anti-PA antibodies (IgG and IgM in the serum and IgA in nasal and lung mucosal secretions) and the proliferation of splenocytes after in vitro stimulation. The anti-PA IgG subtype induced was mainly IgG1. Finally, anthrax lethal toxin neutralization activity was detected both in the serum and in the mucosal secretions.


CONCLUSIONS
The anti-PA immune response induced by nasal PA incorporated in LPD was comparable to that induced by nasal PA adjuvanted with cholera toxin or subcutaneously injected PA adjuvanted with aluminum hydroxide.
Sloat
Brian R
BR
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, 97331, USA.
Cui
Zhengrong
Z
D000281:Administration, Intranasal; D000818:Animals; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007070:Immunoglobulin A / Q000096:biosynthesis; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011479:Protamines; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology* / Q000493:pharmacokinetics
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D007070:Immunoglobulin A; D008081:Liposomes; D011479:Protamines; D019444:Vaccines, DNA