Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates.

BACKGROUND: Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. RESULTS: Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. CONCLUSIONS: Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases.

Monitoring and mitigating isoflurane emissions during inhalational anesthesia of mice.

Establishing a program to monitor waste anesthetic gas (WAG) in order to limit personnel exposure requires measuring the levels of WAG emitted and determining the effectiveness of scavenging methods to reduce such levels. In this study, the authors used infrared spectroscopy to measure levels of WAG emitted while anesthetizing mice with isoflurane for 15 min. They evaluated four different WAG scavenging conditions during induction and maintenance anesthesia: two conditions that used passive techniques and two that used active techniques. Isoflurane concentrations were measured at three different locations: in the operator's vicinity, at the mouse-facemask interface and in the room environment. Passive scavenging of WAG improved when chambers were purged with oxygen after induction and when a diaphragm-sealed facemask delivered a reduced anesthetic flow rate during maintenance anesthesia. Active scavenging of WAG improved when a relief intake opening was provided in the induction chamber's vacuum line, vacuum draw after induction was regulated and the anesthetic flow rate and vacuum scavenging draw were balanced during maintenance anesthesia using a facemask that separated the breathing space from the scavenging zone. Additionally, time-weighted average isoflurane WAG levels detected by personal dosimeters correlated with real-time measurements made using infrared spectroscopy. These observations contribute to the development of a substantiated program for monitoring WAG air quality.