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Rapid Vaccination Using an Acetalated Dextran Microparticulate Subunit Vaccine Confers Protection Against Triplicate Challenge by Bacillus Anthracis

Abstract

Purpose

A rapid immune response is required to prevent death from Anthrax, caused by Bacillus anthracis.

Method

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.

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Abbreviations

/MP:

encapsulated in Ac-DEX microparticles

Ac-DEX:

acetalated dextran

APCs:

antigen presenting cell

AVA:

anthrax vaccine absorbed

B. anthracis :

Bacillus anthracis

CD*+:

cluster designation 8 T cell (cyotoxic T cell)

CD4+:

cluster designation 4 T cell (helper T cell)

CDC:

Centers for Disease Control

CFUs:

colony forming units

DC:

dendritic cell

DMSO:

dimethyl sulfoxide

ED50:

effective dose where 50% inhibition is achieved

EE:

encapsulation efficiency

EF:

edema factor

i.t.:

intratracheal

IFN:

interferon

IL:

interlukein

LeTx:

leathal anthrax toxin

LF:

lethal factor

LPS:

lipopolysaccharide

MHC:

major histocompatibility complex

MP:

micropartilces

PA:

protective antigen

PBS:

phosphate buffer solution

PLGA:

poly(lactic-co-glycolic acid)

PVA:

poly vinyl alcohol

Resiq:

resiquimod

rLF:

recombinent lethal factor

rPA:

recombinent protective antigen

TEA:

triethylamine

Th2:

type two helper T cell

TLR:

toll-like receptor

TNA:

toxin neutralization assay

VLP:

virus-like particle

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Acknowledgments AND DISCLOSURES

The authors would like to thank our funding source DAPRA Grant W911NF-10-1-0264. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government.

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Correspondence to Kristy M. Ainslie.

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Schully, K.L., Sharma, S., Peine, K.J. et al. Rapid Vaccination Using an Acetalated Dextran Microparticulate Subunit Vaccine Confers Protection Against Triplicate Challenge by Bacillus Anthracis . Pharm Res 30, 1349–1361 (2013). https://doi.org/10.1007/s11095-013-0975-x

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KEY WORDS

  • anthrax
  • bacterial vaccine
  • inhalation anthrax
  • polymeric nanoparticle/microparticle
  • vaccine