Rapid vaccination using an acetalated dextran microparticulate subunit vaccine confers protection against triplicate challenge by bacillus anthracis.
OBJECTIVE
A rapid immune response is required to prevent death from Anthrax, caused by Bacillus anthracis.


METHODS
We formulated a vaccine carrier comprised of acetalated dextran microparticles encapsulating recombinant protective antigen (rPA) and resiquimod (a toll-like receptor 7/8 agonist).


RESULTS
We were able to protect against triplicate lethal challenge by vaccinating twice (Days 0, 7) and then aggressively challenging on Days 14, 21, 28. A significantly higher level of antibodies was generated by day 14 with the encapsulated group compared to the conventional rPA and alum group. Antibodies produced by the co-encapsulated group were only weakly-neutralizing in toxin neutralization; however, survival was not dependent on toxin neutralization, as all vaccine formulations survived all challenges except control groups. Post-mortem culture swabs taken from the hearts of vaccinated groups that did not produce significant neutralizing titers failed to grow B. anthracis.


CONCLUSIONS
Results indicate that protective antibodies are not required for rapid protection; indeed, cytokine results indicate that T cell protection may play a role in protection from anthrax. We report the first instance of use of a particulate carrier to generate a rapid protective immunity against anthrax.
Vaccine and Medical Countermeasures Department Biological Defense Research Directorate Naval Medical Research Center, Silver Spring, Maryland 20910, USA.
Kevin L
KL
Schully
Sadhana
S
Sharma
Kevin J
KJ
Peine
John
J
Pesce
Margret A
MA
Elberson
Mariko E
ME
Fonseca
Angela M
AM
Prouty
Matthew G
MG
Bell
Hassan
H
Borteh
Matthew
M
Gallovic
Eric M
EM
Bachelder
Andrea
A
Keane-Myers
Kristy M
KM
Ainslie
D000107:Acetylation; D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D003911:Dextrans / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D051379:Mice; D051193:Toll-Like Receptors / Q000819:agonists; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D003911:Dextrans; D004337:Drug Carriers; D007093:Imidazoles; D051193:Toll-Like Receptors; D022223:Vaccines, Subunit; C030325:anthrax toxin; C402365:resiquimod