Table 1.

Particulate Vaccine Delivery Systems Investigated for Category A Bioterrorism Agents.

Disease	Antigen	Delivery System	Adjuvants	Animal Model	Dosing Scheme	Major Results	Ref.
Anthrax	PA	PLA microparticle	None	Mice	i.m. or i.n., two doses	Complete protection mediated by robust levels of anti-PA IgG	27
	A subunit of PA	PLGA nanoparticle	None	Mice	i.p., single dose	Balanced Th1/Th2 humoral immune responses; prolonged survival compared with a soluble vaccine	28
	PA	Nanoemulsion	None	Mice, guinea pigs	i.n., two doses	More than 3-fold higher anti-PA IgG and IgA titers than vaccines composed of other adjuvants including MPLA, CpG or Alum; protection rates of 70% and 40% following a low and high dose of pathogen challenge, respectively	31
	PA	Chitosan nanoparticle	Compound 48/80	Mice	i.n., three doses	Enhanced mucosal and systemic humoral immune responses compared with soluble vaccines	29
	PA	Liposome	MPLA	Rabbits	i.m., two or three doses	Complete protection mediated by robust levels of neutralizing antibodies	32
	PA	Dextran microparticle	Resiquimod	Mice	s.c., two doses	Complete protection possibly by cellular immune responses	30
	PA	Aluminum nanoparticle	None	Mice	s.c., two doses	Durable anti-PA IgG titer for a month after the booster dose; enhanced antigen uptake, and milder inflammation at the injection site compared with the microparticle counterpart	34
Plague	F1 and LcrV	PLA microparticle	None	Mice	i.t., i.m., or i.n., two doses	Successful elicitation of antigen-specific antibodies	38
	F1	PLGA/PEG microparticle	None	Mice	s.c., single dose	Complete protection mediated by robust anti-F1 IgG titers	39
	B- and T-cell epitopes of LcrV	PLGA microparticle	None	Mice	i.n., single dose	Balanced Th1/Th2 responses; protection rates varied between 0–90% depending on epitope sequences	40
	F1-V	Poly(anhydride) nanoparticle	None	Mice	i.n., single dose	Complete protection mediated by high avidity, antigen-specific IgG	42
Plague	F1	Gold nanoparticle	Alhydrogel®	Mice	s.c., single dose	Two- to four-fold higher titers and avidity of anti-F1 IgG than those elicited by a soluble vaccine or the particulate vaccine without adjuvant	43
	LcrV	Lipoprotein nanoparticle	MPLA or CpG	Mice	i.p., single dose	Four-fold higher anti-V IgG titer than that elicited by soluble vaccines	44
	F1-V	Cationic lipid/hyaluronic acid hybrid nanoparticle	MPLA	Mice	i.n., three doses	Enhanced biocompatibility and 11-fold increase in serum titers of F1-V-specific IgG with balanced Th1/Th2 IgG subtypes	23
Hemorrhagic fever caused by filoviruses	Irradiated whole Ebola virus	Liposome	MPLA	Mice, NHP	i.v. or i.m., two doses	Elicitation of cytotoxic T-lymphocyte responses; complete protection was achieved in the murine but not the NHP model	59, 60
	Ebola GP and VP40	VLP	None	Mice	i.m. or i.p., three doses	Activation of dendritic cells in vitro; elicitation of cellular and humoral immune responses in vivo; complete protection	54
	Ebola GP, NP, and VP40	VLP	Ribi adjuvant	NHP	i.m., three doses	Elicitation of humoral and cellular immune responses; complete protection	55
	Ebola GP, Marburg GP, and VP40	VLP	Poly I:C	Guinea pigs	Unknown route, two doses	The protection rate against a Marburg viral challenge was higher than 70%; protection rates against an Ebola viral challenge varied between 20%–70% for Ebola GP subunits with different immunogenicity	58
Hemorrhagic fever caused by flaviviruses	WNV envelope protein	Gold nanoparticles of different sizes and shapes	None	Mice	i.p., two doses	Rod-like particles facilitated antigen uptake by antigen-presenting cells, whereas 40-nm nanospheres elicited the highest levels of antigen-specific antibodies and inflammatory cytokines in vivo	65
	WNV envelope protein	PLGA nanoparticle	CpG	Mice	s.c., two doses	Th1-skewed humoral immune responses; a protection rate of 94%.	66
Botulism	Subunit of the botulinum toxin	Pullulan nanogel	None	Mice	i.n., single dose	Prolonged nasal residence of the antigen within 12 h post immunization; robust titers of antigen-specific mucosal IgA and systemic IgG; complete protection	72
Tularemia	Membrane proteins of LVS	Liposome	IL-12 and Alum	Mice	s.c, i.p., or i.n., three doses	Complete protection against LVS but not a virulent strain	73
	LVS lysates	Catanionic vesicle	None	Mice	s.c, i.p., or i.n., two to four doses	Protection rates were 100% and < 25% against LVS and a virulent strain, respectively	74

Abbreviations: PA, the protective antigen of Bacillus anthracis; PLA, poly-L-lactide; PLGA, poly(lactic-co-glycolic acid); PEG, polyethylene glycol; LcrV: low-calcium response V antigen of Yersinia pestis; F1-V, recombinant protein of capsular portion F1 and LcrV of Yersinia pestis; MPLA, monophosphoryl lipid A; LVS, live vaccine strain of attenuated Francisellar tularensis; GP, glycoprotein; NP, nucleoprotein; VP40, viral matrix protein 40 of filoviruses; VLP, virus-like particle; poly I:C, polyinosinic-polycytidylic acid; NHP, non-human primate; WNV, West Nile virus; i.m., intramuscular; i.n., intranasal; i.p., intraperitoneal; s.c., subcutaneous, i.t., intratracheal; i.v., intravenous.