Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.
The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.
Huang
Joanne
J
BD Technologies, North Carolina 27709, USA.
D'Souza
Ajit J
AJ
Alarcon
Jason B
JB
Mikszta
John A
JA
Ford
Brandi M
BM
Ferriter
Matthew S
MS
Evans
Michelle
M
Stewart
Todd
T
Amemiya
Kei
K
Ulrich
Robert G
RG
Sullivan
Vincent J
VJ
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D005260:Female; D005612:Freeze Drying; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D051379:Mice; D010930:Plague / Q000517:prevention & control*; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology*; D011208:Powders; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016019:Survival Analysis; D014614:Vaccines, Synthetic; D015010:Yersinia pestis / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011208:Powders; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C086725:caf1 protein, Yersinia pestis