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Resource and Technical AdvanceIn-Press PreviewCOVID-19Vaccines Open Access | 10.1172/jci.insight.169860

A modeling-based approach to optimize COVID-19 vaccine dosing schedules for improved protection

Prashant Dogra,1 Carmine Schiavone,2 Zhihui Wang,1 Javier Ruiz-Ramírez,3 Sergio Caserta,2 Daniela I. Staquicini,4 Christopher Markosian,4 Jin Wang,5 H. Dirk Sostman,6 Renata Pasqualini,4 Wadih Arap,7 and Vittorio Cristini1

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Dogra, P. in: JCI | PubMed | Google Scholar |

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Schiavone, C. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Wang, Z. in: JCI | PubMed | Google Scholar |

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Ruiz-Ramírez, J. in: JCI | PubMed | Google Scholar |

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Caserta, S. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Staquicini, D. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Markosian, C. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Wang, J. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Sostman, H. in: JCI | PubMed | Google Scholar |

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Pasqualini, R. in: JCI | PubMed | Google Scholar

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Arap, W. in: JCI | PubMed | Google Scholar |

1Mathematics in Medicine Program, Houston Methodist Research Institute, Houston, United States of America

2Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Naples, Italy

3Centro de Cienci as de la Salud, Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico

4Department of Radiation Oncology, Rutgers University, Newark, United States of America

5Immunobiology and Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston, United States of America

6Medicine, Houston Methodist Research Institute, Houston, United States of America

7Division of Hematology/Medical Oncology, Rutgers University, Newark, United States of America

Find articles by Cristini, V. in: JCI | PubMed | Google Scholar

Published May 25, 2023 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.169860.
Copyright © 2023, Dogra et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 25, 2023 - Version history
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Abstract

While the development of different vaccines slowed the dissemination of SARS-CoV-2, the occurrence of breakthrough infections has continued to fuel the COVID-19 pandemic. To at least secure partial protection in majority of the population through one dose of a COVID-19 vaccine, delayed administration of boosters has been implemented in many countries. However, waning immunity and emergence of new variants of SARS-CoV-2 suggest that such measures may induce breakthrough infections due to intermittent lapses in protection. Optimizing vaccine dosing schedules to ensure prolonged continuity in protection could thus help control the pandemic. We developed a mechanistic model of immune response to vaccines as an in-silico tool for dosing schedule optimization. The model was calibrated with clinical datasets of acquired immunity to COVID-19 mRNA vaccines in healthy and immunocompromised subjects and showed robust validation by accurately predicting neutralizing antibody kinetics in response to multiple doses of COVID-19 mRNA vaccines. Importantly, by estimating population vulnerability to breakthrough infections, we predicted tailored vaccination dosing schedules to minimize breakthrough infections, especially for immunocompromised subjects. We identified that the optimal vaccination schedules vary from CDC-recommended dosing, suggesting that the model is a valuable tool to optimize vaccine efficacy outcomes during future outbreaks.

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View Literature-derived clinical data used for model calibration and validation

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  • Version 1 (May 25, 2023): In-Press Preview

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