Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?

Sep 23, 2026

Uploaded by Aurelia

Immunodeficient humanized immune system (HIS) rodents—mice with human immune cells and, in some variants, human lymphoid tissues—are reviewed for how they recapitulate human immunology and associated responses. HIS models have been used for human-restricted viral infections such as HCMV and HIV and for human cancer immunobiology, addressing differences from conventional murine models. The review highlights HCMV-based vaccine limitations in traditional animal systems and proposes novel HIS mouse and emerging HIS rat models to support mechanistic and long-term vaccinology studies. It emphasizes improved translatability from laboratory findings to clinical application.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

Introduction

Review Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers? Kaci Craft 1, Athina Amanor 1, Ian Barnett 1, Clarke Donaldson 1, Ignacio Anegon 2, Srinivas Madduri 3, Qiyi Tang 1 and Moses T. Bility 1, * Academic Editor: Minolfa C. Prieto Received: 5 March 2025 Revised: 20 March 2025 Accepted: 22 March 2025 Published: 27 March 2025 Citation: Craft, K.; Amanor, A.; Barnett, I.; Donaldson, C.; Anegon, I.; Madduri, S.; Tang, Q.; Bility, M.T. Can Humanized Immune System Mouse andRat Models Accelerate the Development of CytomegalovirusBased Vaccines Against Infectious Diseases and Cancers? Int. J. Mol. Sci. 2025, 26, 3082. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms26073082](10.3390/ijms26073082) Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[licenses/by/4.0/](licenses/by/4.0/)) . 1 Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA; [kaci.craft@bison.howard.edu](kaci.craft@bison.howard.edu) (K.C.); [athina.amanor@bison.howard.edu](athina.amanor@bison.howard.edu) (A.A.); [ian.barnett@bison.howard.edu](ian.barnett@bison.howard.edu) (I.B.); [clarke.donaldson@bison.howard.edu](clarke.donaldson@bison.howard.edu) (C.D.); [qiyi.tang@howard.edu](qiyi.tang@howard.edu) (Q.T.) 2 Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, F-44000 Nantes, France; [ignacio.anegon@univ-nantes.fr](ignacio.anegon@univ-nantes.fr) 3 Bioengineering and Neuroregeneration Laboratory, Department of Surgery, University of Geneva, 1211 Geneva, Switzerland; [srinivas.madduri@unige.ch](srinivas.madduri@unige.ch) * [Correspondence: moses.bility@howard.edu](Correspondence: moses.bility@howard.edu) Abstract: Over the past three decades, immunodeficient mouse models carrying human immune cells, with or without human lymphoid tissues, termed humanized immune system (HIS) rodent models, have been developed to recapitulate the human immune system and associated immune responses. HIS mouse models have successfully modeled many human-restricted viral infections, including those caused by human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV) . HIS mouse models have also been used to model human cancer immunobiology, which exhibits differences from murine cancers in traditional mouse models. Variants of HIS mouse models that carry human liver cells, lung tissue, skin tissue, or human patient-derived tumor xenografts and human hematopoietic stem cells-derived-human immune cells with or without lymphoid tissue xenografts have been developed to probe human immune responses to infections and human tumors. HCMV-based vaccines are human-restricted, which poses limitations for mechanistic and efficacy studies using traditional animal models. The HCMV-based vaccine approach is a promising vaccine strategy as it induces robust effector memory T cell responses that may be critical in preventing and rapidly controlling persistent viral infections and cancers. Here, we review novel HIS mouse models with robust human immune cell development and primary and secondary lymphoid tissues that could address many of the limitations of HIS mice in their use as animal models for HCMV-based vaccine research. We also reviewed novel HIS rat models, which could allow long-term (greater than one year) vaccinology studies and better recapitulate human pathophysiology. Translating laboratory research findings to clinical application is a significant bottleneck in vaccine development; HIS rodents and related variants that more accurately model human immunology and diseases could increase the translatabil

FAQs

What are humanized immune system (HIS) rodent models used for?

They use immunodeficient mice or other HIS rodents carrying human immune cells, sometimes with lymphoid tissues, to recapitulate human immune responses relevant to infections and cancer.

Why are HCMV-based vaccines challenging to study with traditional animal models?

HCMV-based vaccines are human-restricted, which limits mechanistic and efficacy studies using species-restricted traditional models.

How do novel HIS mouse and HIS rat models improve vaccine research?

They are designed to provide robust human immune cell development and primary/secondary lymphoid tissues, and HIS rat models may enable long-term vaccinology studies that better reflect human pathophysiology.

Sep 23, 2026

Uploaded by Aurelia