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In Vivo Assay for Detection of Antigen-specific T-cell Cytolytic Function Using a Vaccination Model
Published on: November 28, 2017
Application of median lethal concentration (LC50) of pathogenic microorganisms and their antigens in vaccine
1Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Federal University of Agriculture, P.M.B. 2373, Makurdi, Benue, Nigeria. pharm_saga2006@yahoo.com.
Objective:
Lack of ideal mathematical models to qualify and quantify both pathogenicity, and virulence is a dreadful setback in development of new antimicrobials and vaccines against resistance pathogenic microorganisms. Hence, the modified arithmetical formula of Reed and Muench has been integrated with other formulas and used to determine bacterial colony forming unit/viral concentration, virulence and immunogenicity.
Results:
Microorganisms' antigens tested are Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa in mice and rat, Edwardsiella ictaluri, Aeromonas hydrophila, Aeromonas veronii in fish, New Castle Disease virus in chicken, Sheep Pox virus, Foot-and-Mouth Disease virus and Hepatitis A virus in vitro, respectively. The LC50s for the pathogens using different routes of administrations are 1.93 × 103(sheep poxvirus) and 1.75 × 1010 for Staphylococcus aureus (ATCC29213) in rat, respectively. Titer index (TI) equals N log10 LC50 and provides protection against lethal dose in graded fashion which translates to protection index. N is the number of vaccine dose that could neutralize the LC50. Hence, parasite inoculum of 103 to 1011 may be used as basis for determination of LC50 and median bacterial concentrations (BC50).Pathogenic dose for immune stimulation should be sought at concentration about LC10.
Insights
Developing new antimicrobials and vaccines is hindered by a lack of models for pathogenicity and virulence. This study integrates modified formulas to quantify these factors, aiding in the development of effective countermeasures against resistant pathogens.
Area of Science:
- Microbiology and Immunology
- Mathematical Modeling in Life Sciences
- Vaccine Development
Background:
- Current mathematical models are inadequate for quantifying pathogenicity and virulence of microorganisms.
- This limitation significantly impedes the development of novel antimicrobials and vaccines.
- Addressing this gap is crucial for combating drug-resistant pathogenic microorganisms.
Purpose of the Study:
- To develop and apply an integrated mathematical model for quantifying microbial pathogenicity and virulence.
- To determine bacterial colony-forming units, viral concentrations, virulence, and immunogenicity.
- To establish a basis for calculating lethal dose 50% (LC50) and median bacterial concentrations (BC50).
Main Methods:
- Integration of the modified Reed and Muench formula with other mathematical models.
- Application of the model to various bacterial and viral pathogens across different animal models (mice, rats, fish, chickens) and in vitro.
- Calculation of Titer Index (TI) using LC50 values to determine vaccine efficacy and protection levels.
Main Results:
- Successfully determined LC50 values for pathogens like Sheep Poxvirus (1.93 × 10^3) and Staphylococcus aureus (1.75 × 10^10).
- Introduced the Titer Index (TI = N log10 LC50) as a measure of protection against lethal doses.
- Proposed that parasite inoculum ranging from 10^3 to 10^11 can serve as a basis for LC50 and BC50 determination.
Conclusions:
- The integrated mathematical model provides a robust framework for quantifying pathogenicity and virulence.
- The Titer Index offers a graded measure of protection, facilitating vaccine efficacy assessment.
- Pathogenic dose for immune stimulation should be investigated around the LC10 concentration.
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