CVI Accepts, published online ahead of print on 4 March 2009

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Clin. Vaccine Immunol. doi:10.1128/CVI.00447-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine

Joanne Huang, Ajit J. D'Souza, Jason B. Alarcon, John A. Mikszta, Brandi M. Ford, Matthew S. Ferriter, Michelle Evans, Todd Stewart, Kei Amemiya, Robert G. Ulrich, and Vincent J. Sullivan^*

BD Technologies, 21 Davis Drive, RTP, NC 27709, USA; United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Frederick, MD, 21702

^* To whom correspondence should be addressed. Email: vince_sullivan{at}bd.com.

The potential use of Y. 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 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 IM injection, microneedle-based intradermal delivery or non-invasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against 1000 LD50 Y. pestis lethal subcutaneous challenge at levels equivalent to those elicited by unprocessed liquid formulations (70 – 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 compared 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 appears to be a better predictor of protection against Y. pestis challenge than seroconversion against either F1V or V.

In summary, we demonstrate the pre-clinical feasibility of using 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 powder vaccine formulation may result in substantial health and economic benefits.