Influence of Intravenous Anesthesia on Mucosal and Systemic Antibody Responses to Nasal Vaccines

Abstract

Inhalation of antigens may stimulate the immune system by way of the upper as well as the lower airways. We have shown that at least 1,000 times more live pneumococci were recovered from pulmonary tissue after being presented as drops of a liquid suspension onto the nares of anesthetized mice compared to the number of bacteria recovered from animals that were not anesthetized in the course of the challenge. Mice that were similarly immunized intranasally by inhalation of three different nonreplicating particulate vaccine formulations, i.e., a meningococcal outer membrane vesicle (OMV) vaccine, a formalin-inactivated whole-virus influenza (INV) vaccine, and the INV vaccine with OMVs as a mucosal adjuvant, during general intravenous anesthesia developed concentrations of vaccine-specific serum immunoglobulin G (IgG) antibodies that were four to nine times higher than in mice that were fully awake during immunizations. The concentrations of IgA antibodies in serum were also higher in anesthetized than in nonanesthetized mice and correlated positively with the corresponding levels of serum IgG antibodies in the anesthetized but not in the nonanesthetized mice. In saliva and feces, however, the concentrations of IgA antibodies were equally high whether or not the animals were dormant during immunizations. The results indicate that intrapulmonary antigen presentation, as a part of an intranasal immunization strategy, is of importance for systemic but not for mucosal antibody responses. A major portion of IgA antibodies in serum may thus be derived from nonmucosal sites.

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.…”

Strong Mucosal and Systemic Immunities Induced by Nasal Immunization with Anthrax Protective Antigen Protein Incorporated in Liposome–Protamine–DNA Particles

“…In nasal immunization, it is known that the nasally dosed vaccine has a great potential to be inhaled into the lung. Lung involvement usually led to a stronger specific immune response, but can potentially cause serious proinflammatory response in the lung, and thus limit its use in humans (19,36,37). With our dosing technique and FITC-labeled rPA /LPD, we have confirmed that nasally dosed FITC-labeled rPA/LPD mainly remained in the nare passages 4 h after dosing, while it was not detectable in the lung washes (data not shown), suggesting that the contribution from lung immunization to the induced PA-specific immune response was limited.…”

Intranasal Immunization Strategy To Impede Pilin-Mediated Binding ofPseudomonas aeruginosato Airway Epithelial Cells

“…The use of isoflurane for i.n. administration results in suppression of the swallowing reflex and facilitates preferential delivery to the trachea rather than the esophagus (27). Negative control animals received an equal volume of carrier buffer (PBS) by i.n.…”