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Inducing Meningococcal Meningitis Serogroup C in Mice via Intracisternal Delivery
Published on: November 5, 2019
Modeling protective meningococcal antibody responses and factors influencing antibody persistence following
Md Nasir1, William B Weeks1, Shahrzad Gholami1
1AI for Good Lab, Microsoft, Redmond, Washington, United States of America.
Abstract:
Meningococcal meningitis poses a significant public health burden in the meningitis belt region of sub-Saharan Africa. The introduction of the meningococcal PsA-TT vaccine (MenAfriVac®) has successfully eliminated Neisseria meningitidis serogroup A (NmA) cases in the region. However, the duration of post-vaccination immunity and the need for booster doses remain uncertain. To address this knowledge gap, we developed computational models using machine learning techniques to improve the effectiveness of modeling in guiding vaccination strategies for the African meningitis belt. Using serologic data from previous clinical trials of PsA-TT, we proposed a short-term and a long-term model that integrated demographic and medical variables (such as age, height and weight) with previous antibody titer levels and vaccination information to predict NmA antibody titer levels following vaccination. In the short-term model, we found moderately high performance (R-squared = 0.59) for out-of-training-data subjects and even better performance (R squared = 0.83) in the long-term evaluation. Our models estimated the half-life of the vaccine to be 13.9 years for the study population overall, similar to previously reported estimates. Machine learning techniques offer several advantages over previous approaches, as they do not require multiple readings from the same subject, can be rigorously validated using a subset of subject data not used for training. The proposed approach also facilitates the interpretation of the relationship between input variables and antibody levels at a population level. By incorporating subject-specific demographic and medical variables, our models could potentially be used to tailor vaccination schedules to at-risk populations.
Insights
Machine learning models predict Neisseria meningitidis serogroup A (NmA) antibody levels after vaccination, estimating a vaccine half-life of 13.9 years. This aids in optimizing vaccination strategies for the African meningitis belt.
Area of Science:
- Epidemiology
- Immunology
- Computational Biology
Background:
- Meningococcal meningitis is a major health concern in sub-Saharan Africa's meningitis belt.
- The meningococcal PsA-TT vaccine (MenAfriVac®) has eliminated Neisseria meningitidis serogroup A (NmA) cases.
- Uncertainty remains regarding the duration of vaccine immunity and the need for booster doses.
Purpose of the Study:
- To develop computational models using machine learning to predict NmA antibody titer levels.
- To guide vaccination strategies for the African meningitis belt by understanding vaccine immunity duration.
- To integrate demographic and medical variables with serologic data for improved predictive modeling.
Main Methods:
- Developed short-term and long-term computational models using machine learning.
- Integrated demographic (age, height, weight) and medical variables with antibody titer data.
- Utilized serologic data from previous clinical trials of the PsA-TT vaccine.
Main Results:
- Short-term model achieved R-squared of 0.59 for out-of-training data.
- Long-term model evaluation showed improved performance with R-squared of 0.83.
- Estimated vaccine half-life at 13.9 years for the study population.
Conclusions:
- Machine learning models offer advantages in predicting antibody levels and validating data.
- The models facilitate understanding of variable relationships influencing antibody levels.
- Incorporating individual data can help tailor vaccination schedules for at-risk populations.
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