Abstract A64: Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2
Authors: Voutouri Chrysovalantis , Hardin Corey C , Naranbhai Vivek , Nikmaneshi Mohammad R. , Khandekar Melin J. , Gainor Justin F , Stylianopoulos Triantafyllos , Munn Lance L. , Jain Rakesh K. 
Published: December 2022

Abstract
Introduction: Current SARS-CoV-2 vaccines are effective at preventing COVID-19 or limiting disease severity in healthy individuals, but effectiveness is lower among patients with cancer or immunosuppression. Vaccine effectiveness wanes with time and varies by vaccine type. Moreover, current vaccines are based on the ancestral SARS-CoV-2 spike protein sequence and emerging viral variants evade vaccine induced immunity. Booster doses partially overcome these issues, but there are limited clinical data on the durability of protection afforded by boosters – especially against SARS-CoV-2 variants.Methods: Here we describe a mechanistic mathematical model for vaccination-induced immunity and use it to predict vaccine effectiveness taking into account current and possible future viral, host and vaccine characteristics. Crucially, this allows predictions over time frames currently not reported in the clinical literature. The model incorporates the infection of lung epithelium by SARS-CoV-2, the response of innate and adaptive immune cells to infection, the production of pro-and anti-inflammatory cytokines, the activation of the coagulation cascade, as well as the effects of cancer cells on the lung and on the immune response. The model further accounts for the interactions between the virus, the immune cells and the tumor cells as well as for vaccination-induced immunity.Results: Model predictions were validated with clinical data. The model predicts that for healthy individuals vaccinated and boosted with mRNA-1273, BNT-162b2a, and Ad26.COV2.S, robust immunogenicity against the ancestral and delta variant extends beyond a year. Immunogenicity is also enhanced following booster vaccination in patients with cancer on various anti-cancer therapies, including immunotherapy, and for patients without cancer on immunosuppressive agents.Conclusion: Our model predicts that ³1 booster doses will be required for these individuals to maintain protective immunity. Furthermore, for immunosuppressed individuals, simulated new SARS-CoV2 variants with enhanced ability to bind to target cells, faster replication or reduced immunogenicity could lead to breakthrough infections even after a single booster dose. Modelling data such as these may be used to anticipate and plan for future vaccination needs.
Citation Format: Chrysovalantis Voutouri, Corey C Hardin, Vivek Naranbhai, Mohammad R. Nikmaneshi, Melin J. Khandekar, Justin F Gainor, Triantafyllos Stylianopoulos, Lance L. Munn, Rakesh K. Jain. Mechanistic model for booster doses effectiveness in healthy, cancer and immunosuppressed patients infected with SARS-CoV-2 [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A64.