Brian R Sloat

Publications (22)84.35 Total impact

• Article: Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized mice.

  Brian R Sloat, Zhengrong Cui
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  ABSTRACT: To better protect against inhalational anthrax infection, a nasal anthrax vaccine based on the protective antigen (PA) protein of Bacillus anthracis could be an attractive alternative to the current Anthrax-Vaccine-Adsorbed (AVA), which was licensed for cutaneous anthrax prevention. Previously, we have demonstrated that an anti-PA immune response comparable with that in mice subcutaneously immunized with PA protein adjuvanted with aluminium hydroxide was induced in both the systemic compartment and the mucosal secretions of the nose and lung of anaesthetized mice when they were nasally immunized with PA protein incorporated into previously reported LPD (Liposome-Protamine-DNA) particles. In this study, we evaluated the anti-PA immune response induced by the nasal PA/LPD particles in non-anaesthetized mice and compared it with that in anaesthetized mice. Our data showed that the anti-PA antibody response and the anthrax lethal toxin-neutralization activity induced by the nasal PA/LPD in non-anaesthetized mice was relatively weaker than that in anaesthetized mice. However, the splenocytes isolated from the nasally immunized mice, anaesthetized and non-anaesthetized, proliferated comparably after in-vitro re-stimulation. By evaluating the uptake of fluorescence-labelled LPD particles by phagocytes in the nasal and broncho-alveolar lavages of mice after the nasal administration, we concluded that the relatively weaker anti-PA immune response in the non-anaesthetized mice might be partially attributed to the reduced retention of the PA/LPD particles in the nasal cavity of the non-anaesthetized mice. Data collected in this study are expected to be useful for future anthrax nasal vaccine studies when mice are used as a model.
  Journal of Pharmacy and Pharmacology 05/2006; 58(4):439-47. · 2.17 Impact Factor
• Article: Strong mucosal and systemic immunities induced by nasal immunization with anthrax protective antigen protein incorporated in liposome-protamine-DNA particles.

  Brian R Sloat, Zhengrong Cui
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  ABSTRACT: The very lengthy and complicated dosing schedule of the current anthrax vaccine adsorbed, which was licensed in the USA for the prevention of cutaneous anthrax infection, calls for the development of an efficacious and easily administrable vaccine to prevent against the most lethal form of anthrax infection, the inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein carried by liposome-protamine-DNA (LPD) particles. PA was incorporated in LPD particles and nasally dosed to mice. The resulting PA-specific immune response and lethal toxin neutralization activity were measured. Mice nasally immunized with PA incorporated into LPD particles developed both systemic and mucosal anti-PA responses. The anti-PA immunities induced included the production of anti-PA antibodies (IgG and IgM in the serum and IgA in nasal and lung mucosal secretions) and the proliferation of splenocytes after in vitro stimulation. The anti-PA IgG subtype induced was mainly IgG1. Finally, anthrax lethal toxin neutralization activity was detected both in the serum and in the mucosal secretions. The anti-PA immune response induced by nasal PA incorporated in LPD was comparable to that induced by nasal PA adjuvanted with cholera toxin or subcutaneously injected PA adjuvanted with aluminum hydroxide.
  Pharmaceutical Research 03/2006; 23(2):262-9. · 4.09 Impact Factor