Protective Immunity in Mice Achieved with Dry Powder Formulation and Alternative Delivery of Plague F1-V Vaccine

Abstract

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-freezedried 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.

Microneedle-Based Intradermal Delivery Enables Rapid Lymphatic Uptake and Distribution of Protein Drugs

“…Stainless steel microneedles are capable of delivering clinically meaningful doses, both volumetrically and on a mass basis. We have previously used microneedles to administer numerous vaccines in pre-clinical models (21)(22)(23)(24)(25)(26), and these devices have also progressed through Phase I-III clinical trials for influenza vaccines (27)(28)(29)(30) with product licensure obtained in Europe (31).…”

Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques

“…1 A and B) (21)(22)(23)(24) were used for delivery. To deliver MVDP to free-breathing macaques, the devices were connected with silicone-based masks (Puff-mask and Sol-mask) that covered the mouth and nose and provided a seal to reduce loss.…”

Routes of Delivery for Biological Drug Products

“…Delivery of proteins using microneedles resulted in faster systemic availability and increased maximal drug concentration over SC Rat full-thickness skin Human heat-stripped skin Pig full-thickness skin Human full-thickness skin, human heat-stripped skin Human full-thickness skin Pig full-thickness skin Rat Rat Mouse, rat, rabbit, pig Mouse delivery for all proteins tested. The same group has previously used microneedles to administer numerous vaccines in preclinical models [259][260][261][262][263][264], and these devices have also progressed through phase I to III clinical trials for influenza vaccines [265][266][267][268] with product licensure obtained in Europe [269].…”