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Hall, Jonah Brooks

University of British Columbia

I used mechanistic ordinary differential equations (ODEs) to model the maternal and neonatal immune responses to pertussis (Tdap) immunization. I recapitulated the dynamics of IgG, long and short-lived plasma cells (PCs), memory B cells, and immune complexes and used their results as a metric of short and long-term protection against pertussis. I developed a metric of the risk of severe infection in neonates that incorporated the protection of maternal origin IgG and used it to optimize the timing of the maternal vaccination as well as the first and second shots of the neonatal vaccination series. I found that vaccinating in the 32nd week of pregnancy (𝑡ᵥₘ = −76 𝑑𝑎𝑦𝑠) resulted in the lowest short-term risk posed to neonates in the first year of life. I found that vaccinating neonates as late as possible (10 months) and with a significant gap in between immunizations had a potential benefit to short-term immunity. When using this thesis’ metric of risk I found that neonates from unvaccinated mothers benefit from an initial vaccination date of 109 days after birth (compared to 120 in North America). I modeled the significant effect that maternal antibody interference has on neonatal immune dynamics and contrasted its hindering effect with its short-term protection of neonates. The model suggests a clear increase in the overall risk of a severe pertussis infection in the first year of life in a neonate born to an unvaccinated mother compared to that of a vaccinated mother. I found that despite a lack of quantifiable calculation of necessary parameters in the model, one can still recapitulate the dynamics of pertussis to a relative degree of accuracy and give effective insights into the optimization of the pertussis vaccination strategy. Future clinical work into the estimation of the rates of IgG production by plasma cells, the composition of the B cell population, and the clearance of immune cells and complexes would have a significant impact on increasing the accuracy of the model and of similar equations representing complex immune processes.

Text; Still Image

2023-08-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/85758

Mathematics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/