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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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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DOI: https://doi.org/10.1007/s11095-013-0975-x