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

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.

Effective induction of protective systemic immunity with nasally administered vaccines adjuvanted with IL-1

“…More importantly, nasal immunization of rabbits anesthetized with ketamine + xylazine induced reproducible serum anti-PA IgG and elevated lethal toxin neutralizing titers. Our rabbit results agree with results reported for mice since the use of deep anesthesia enhanced the immunogenicity of nasally delivered vaccines in mice[48, 49]. A major issue that we currently face is how to translate our observations using nasal immunization of anesthetized rabbits into the development and optimization of effective nasal vaccines and nasal immunization strategies for use in humans.…”

“…The use of anesthesia is known to enhance the immunogenicity of nasally delivered vaccines in mice [48, 49], including studies that have utilized anthrax protective antigen as the immunogen. However, the impact the use of anesthetics has on the efficacy of nasal immunization in rabbits is not known.…”

“…The use of anesthesia with nasal immunization has been reported to augment antigen-specific immune responses in mice, including anti-anthrax protective antigen (PA) antibody responses as well as anthrax lethal toxin neutralizing activity [48, 49]. The anesthetic agents that augmented the vaccine-induced immune responses were agents such as propofol and pentobarbital and were delivered by needle injection.…”

Nasal Immunization with Anthrax Protective Antigen Protein Adjuvanted with Polyriboinosinic–Polyribocytidylic Acid Induced Strong Mucosal and Systemic Immunities

“…However, when the dose was decreased to 10 mL, they mainly remained in the nare passages (38). Our previous study also showed that when an FITC-labeled liposome suspension was nasally administered to mice by using the same procedure used in this study (i.e., a total of 20 mL was given separately as two 10-mL doses with 10Y15 min between doses), the majority of FITC-labeled liposomes were recovered in mouse nasal washes 4 h later; whereas FITC-labeled liposomes were not detected in the lung washes (39). In future studies, FITC-labeled PA protein, admixed with pI:C, will be dosed nasally into mice to track PA proteins that reach the lungs.…”

The anthrax vaccine: No new tricks for an old dog

“…39 In the future, it is possible that vaccination will occur via intranasal inoculations, as recent publications demonstrated that mucosal anthrax immunization induces antibody production in both the systemic and secretory-excretory compartments (i.e., saliva, vaginal fluid, respiratory lavages or fecal extracts). [43][44][45][46][47][48][49] In 2002, the National Institute of Allergy and Infectious Diseases emphasized the need for the continued development of anthrax vaccine candidates. Ideally, the new candidates should: (1) confer protection against inhalational anthrax; (2) be administered within three or fewer doses; (3) have shorter administration time; and (4) offer increased safety.…”