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Featured researches published by Vincent J. Sullivan.


The Journal of Infectious Diseases | 2005

Protective Immunization against Inhalational Anthrax: A Comparison of Minimally Invasive Delivery Platforms

John A. Mikszta; Vincent J. Sullivan; Cheryl H. Dean; Andrea Waterston; Jason B. Alarcon; John P. Dekker; John M. Brittingham; Juan Huang; Matthew S. Ferriter; Ge Jiang; Kevin D. Mar; Kamal U. Saikh; Bradley G. Stiles; Chad J. Roy; Robert G. Ulrich; Noel G. Harvey

A new anthrax vaccine under clinical investigation is based on recombinant Bacillus anthracis protective antigen (rPA). Here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rPA in mice and rabbits. In mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection. Intranasal (inl) delivery of a liquid formulation required 3 doses to achieve responses that were comparable with those achieved via the id or im routes. In rabbits, id delivery provided complete protection against aerosol challenge with anthrax spores; in addition, novel powder formulations administered inl provided complete protection, whereas a liquid formulation provided only partial protection. These results demonstrate, for the first time, that cutaneous or nasal mucosal administration of rPA provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combinations described here have the potential to improve the efficacy of rPA and other biodefense vaccines.


Infection and Immunity | 2006

Microneedle-Based Intradermal Delivery of the Anthrax Recombinant Protective Antigen Vaccine

John A. Mikszta; John P. Dekker; Noel G. Harvey; Cheryl H. Dean; John M. Brittingham; Joanne Huang; Vincent J. Sullivan; Beverly Dyas; Chad J. Roy; Robert G. Ulrich

ABSTRACT The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 μg of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.


Expert Opinion on Drug Delivery | 2006

Noninvasive delivery technologies: respiratory delivery of vaccines

Vincent J. Sullivan; John A. Mikszta; Philippe Laurent; Juan Huang; Brandi M. Ford

This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements. Current delivery systems in development for both routes are reviewed herein. The storage and respiratory delivery of drugs and vaccines in powder form has been shown to provide improved stability and extended retention time in the respiratory mucosa. These features, in addition to the noninvasive nature of respiratory delivery, can provide benefits to public health vaccination campaigns, facilitating mass vaccination without the high cost of maintaining cold-chain storage.


Clinical and Vaccine Immunology | 2009

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

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

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-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.


Human Vaccines | 2007

Intranasal Administration of Dry Powder Anthrax Vaccine Provides Protection Against Lethal Aerosol Spore Challenge

Joanne Huang; John A. Mikszta; Matthew S. Ferriter; Ge Jiang; Noel G. Harvey; Beverly Dyas; Chad J. Roy; Robert G. Ulrich; Vincent J. Sullivan

The use of an aerosolizable form of anthrax as a biological weapon is considered to be among the most serious bioterror threats. Intranasal (IN) delivery of a dry powder anthrax vaccine could provide an effective and non-invasive administration alternative to traditional intramuscular (IM) or subcutaneous (SC) injection. We evaluated a dry powder vaccine based on the recombinant Protective Antigen (rPA) of Bacillus anthracis for vaccination against anthrax via IN immunization in a rabbit model. rPA powders were formulated and administered IN using a prototype powder delivery device. We compared serum IgG and toxin neutralizing antibody (TNA) titers of rabbits immunized IN with 10 μg rPA of a powder formulation with those immunized with the same dose of liquid rPA vaccine, delivered either IN or by IM injection. In addition, each group was tested for survival after aerosol spore challenge. Our results showed that IN vaccination with rPA powders elicited serum PA-specific IgG and TNA titers that were equivalent to those raised by liquid rPA administered IN. Serum PA-specific IgG and TNA titers after IN delivery were lower than for IM injection, however, after aerosol spore challenge, rabbits immunized IN with powders displayed 100% protection versus 63% for the group immunized IN with the liquid vaccine and 86% for the group immunized by IM injection. The results suggest that an IN powder vaccine based on rPA is at least as protective as a liquid delivered by IM injection.


Journal of Pharmaceutical Sciences | 2013

Rapid Deamidation of Recombinant Protective Antigen when Adsorbed on Aluminum Hydroxide Gel Correlates with Reduced Potency of Vaccine

Ajit Joseph M. D'Souza; Kevin D. Mar; Joanne Huang; Sumit Majumdar; Brandi M. Ford; Beverly Dyas; Robert G. Ulrich; Vincent J. Sullivan

Deamidation of the recombinant protective antigen (rPA) correlates with decreased effectiveness of the vaccine in protecting against infection by Bacillus anthracis. We present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rPA adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rPA stored in solution without adjuvant. Although deamidation did not impact total levels of rPA-specific antibodies in a mouse model, it did correlate with a decrease in toxin-neutralizing antibodies. On the basis of these data, we hypothesize that interactions of rPA with aluminum hydroxide gel are destabilizing and are the direct cause of reduced vaccine efficacy.


Aerosol Science and Technology | 2012

Deposition of Dry Powder Generated by Solovent in Sophia Anatomical Infant Nose-Throat (SAINT) Model

Beth L. Laube; Gail Sharpless; Charles Shermer; Vincent J. Sullivan; Kenneth G. Powell

Purpose: To quantify deposition of 99mtechnetium-labeled powder in the Sophia Anatomical Infant Nose-Throat (SAINT) model of a 9-month old. Methods: Powder was generated by the Solovent (BD Technologies), an active dry powder inhaler with spacer, during 30 seconds of tidal volume (TV) breathing. Activity that passed through the model was captured on a filter and represented powder that was available for deposition in the lungs. Deposition in the nasal cavity, on the filter, and in the spacer was expressed as a percentage of the injected dose into the spacer. Results: Mean (± SD) injected dose averaged 89.5 ± 0.09%, 90.3 ± 0.11%, and 91.3 ± 0.05% at 50, 100, and 200 mL TV, respectively. Mean nasal deposition increased significantly from 50 mL to 100 mL and 200 mL TV with 0.60 ± 0.002%, 1.72 ± 0.007%, and 6.75 ± 07.21%, respectively (all p ≤ 0.05). Similarly, mean filter deposition increased significantly from 50 mL to 100 mL to 200 mL with 0.28 ± 0.00%, 1.14 ± 0.00%, and 3.87 ± 0.01%, respectively (all p < 0.05). Mean retention in the spacer was similar at 50 mL (93.38 ± 0.02%) and at 100 mL TV (89.97 ± 0.04%), but decreased significantly to 71.47 ± 0.05% at 200 mL TV (all p < 0.05). Conclusions: These data suggest for the first time the feasibility of delivering a dry powder formulation to infants and toddlers by actively introducing the powder into a spacer. Lung deposition and nasal deposition, as a percent of injected dose, were dependent on tidal volume with deposition increasing with increasing TV. Nevertheless, deposition, as a percent of injected dose, was low in both regions. This was likely due to significant retention in the spacer at all 3 tidal volumes. Copyright 2012 American Association for Aerosol Research


Vaccine | 2004

A novel dry powder influenza vaccine and intranasal delivery technology: induction of systemic and mucosal immune responses in rats

Juan Huang; Robert J. Garmise; Timothy M. Crowder; Kevin D. Mar; Anthony J. Hickey; John A. Mikszta; Vincent J. Sullivan


Journal of Pharmaceutical Sciences | 2006

Anthrax Vaccine Powder Formulations for Nasal Mucosal Delivery

Ge Jiang; Sangeeta B. Joshi; Laura J. Peek; Duane T. Brandau; Juan Huang; Matthew S. Ferriter; Wendy D. Woodley; Brandi M. Ford; Kevin D. Mar; John A. Mikszta; Robert G. Ulrich; Noel G. Harvey; C. Russell Middaugh; Vincent J. Sullivan


Archive | 2003

Medicament respiratory delivery device and method

Robert A. Casper; John M. Snow; David L. Gardner; Vincent J. Sullivan; Anjana Bhuta Wills; Lawrence A. Monahan; Christopher J. Knors

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Ge Jiang

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Juan Huang

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