Abstract
During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics have hampered global vaccine delivery, which is impacting mass vaccination strategies. Recent studies have identified different strategies for vaccine dose administration so that supply constraints issues are diminished. These include increasing the time between consecutive doses in a two-dose vaccine regimen and reducing the dosage of the second dose. We consider both of these strategies in a mathematical modeling study of a non-replicating viral vector adenovirus vaccine in this work. We investigate the impact of different prime-boost strategies by quantifying their effects on immunological outcomes based on simple system of ordinary differential equations. The boost dose is administered either at a standard dose (SD) of 1000 or at a low dose (LD) of 500 or 250 vaccine particles. Results show dose-dependent immune response activity. Our model predictions show that by stretching the prime-boost interval to 18 or 20, in an SD/SD or SD/LD regimen, the minimum promoted antibody (Nab) response will be comparable with the neutralizing antibody level measured in COVID-19 recovered patients. Results also show that the minimum stimulated antibody in SD/SD regimen is identical with the high level observed in clinical trial data. We conclude that an SD/LD regimen may provide protective capacity, which will allow for conservation of vaccine doses.
Highlights
The spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), can be mitigated through safe and effective vaccines
We mathematically model adenovirus-based vaccines using a system of simple ordinary differential equations
Variation in its value significantly affects all population peak values, since it is related to the activation rate of the Th0 population, which activates the rest of the immune response, it is always countered by sensitivity to γv and γt, which are parameters informed by the literature
Summary
The spread of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), can be mitigated through safe and effective vaccines. The ODE-based model introduced in this work is based on the biological signaling pathway of the immune response to vaccination The model includes both cellular and humoral immune system components, including vaccine particles, T helper cells, interferongamma (IFNγ), interleukin 6 (IL6), plasma B-cells, antibody, and cytotoxic T-cells. We have developed a mathematical model of an adenovirus vaccine that considers humoral and cell-mediated immune response mechanisms. We explicitly consider T helper type 0 cells, plasma B-cells, antibody, cytotoxic T-cells, and two central cytokines, including IFNγ and IL6. In Equation (1e) we consider an indirect activation of plasma B-cells by Th0 cells at rate μ52T, and by IL6, which is assumed to have an adjuvanted role in stimulation, α54 Humoral immunity is an antibody-mediated response that occurs when plasma B-cells are activated. When a smaller or larger dose size is chosen, parameters μ21, α61 and μ71 are rescaled
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