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

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Title: Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?
Authors: Craft, Kaci, Amanor, Athina, Barnett, Ian, Donaldson, Clarke, Anegon, Ignacio, Madduri, Srinivas, Tang, Qiyi, Bility, Moses
Contributors: Howard University College of Medicine Washington, DC, USA, Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (Team 2 - U1064 Inserm - CR2TI), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Université de Genève = University of Geneva (UNIGE), R01 AI152655/AI/NIAID NIH HHS/United StatesR01 AI162615/AI/NIAID NIH HHS/United StatesSC1 AI112785/AI/NIAID NIH HHS/United StatesR01AI15265/GF/NIH HHS/United States
Source: ISSN: 1661-6596.
Publisher Information: CCSD
MDPI
Publication Year: 2025
Collection: Université de Nantes: HAL-UNIV-NANTES
Subject Terms: HCMV-based vaccines, HIV vaccines, HIV/AIDS-animal models, human cancer xenograft models, humanized immune system and rats, MESH: Animals, MESH: Cytomegalovirus Infections / immunology, MESH: Rats, MESH: Cytomegalovirus Infections / prevention & control, MESH: Cytomegalovirus Vaccines / immunology, MESH: Cytomegalovirus / immunology, MESH: Disease Models, Animal, MESH: Humans, MESH: Mice, MESH: Neoplasms / immunology, MESH: Neoplasms / prevention & control, [SDV]Life Sciences [q-bio]
Description: International audience ; 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 translatability of research findings.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/40243710; PUBMED: 40243710; PUBMEDCENTRAL: PMC11988357
DOI: 10.3390/ijms26073082
Availability: https://inserm.hal.science/inserm-05117161
https://inserm.hal.science/inserm-05117161v1/document
https://inserm.hal.science/inserm-05117161v1/file/ijms-26-03082.pdf
https://doi.org/10.3390/ijms26073082
Rights: http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.BC349DAE
Database: BASE
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PubType: Academic Journal
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  Data: Can Humanized Immune System Mouse and Rat Models Accelerate the Development of Cytomegalovirus-Based Vaccines Against Infectious Diseases and Cancers?
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  Data: <searchLink fieldCode="AR" term="%22Craft%2C+Kaci%22">Craft, Kaci</searchLink><br /><searchLink fieldCode="AR" term="%22Amanor%2C+Athina%22">Amanor, Athina</searchLink><br /><searchLink fieldCode="AR" term="%22Barnett%2C+Ian%22">Barnett, Ian</searchLink><br /><searchLink fieldCode="AR" term="%22Donaldson%2C+Clarke%22">Donaldson, Clarke</searchLink><br /><searchLink fieldCode="AR" term="%22Anegon%2C+Ignacio%22">Anegon, Ignacio</searchLink><br /><searchLink fieldCode="AR" term="%22Madduri%2C+Srinivas%22">Madduri, Srinivas</searchLink><br /><searchLink fieldCode="AR" term="%22Tang%2C+Qiyi%22">Tang, Qiyi</searchLink><br /><searchLink fieldCode="AR" term="%22Bility%2C+Moses%22">Bility, Moses</searchLink>
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  Data: Howard University College of Medicine Washington, DC, USA<br />Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (Team 2 - U1064 Inserm - CR2TI)<br />Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI)<br />Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE)<br />Nantes Université - pôle Santé<br />Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé<br />Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE)<br />Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)<br />Université de Genève = University of Geneva (UNIGE)<br />R01 AI152655/AI/NIAID NIH HHS/United StatesR01 AI162615/AI/NIAID NIH HHS/United StatesSC1 AI112785/AI/NIAID NIH HHS/United StatesR01AI15265/GF/NIH HHS/United States
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  Data: <i>ISSN: 1661-6596</i>.
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  Data: 2025
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  Data: <searchLink fieldCode="DE" term="%22HCMV-based+vaccines%22">HCMV-based vaccines</searchLink><br /><searchLink fieldCode="DE" term="%22HIV+vaccines%22">HIV vaccines</searchLink><br /><searchLink fieldCode="DE" term="%22HIV%2FAIDS-animal+models%22">HIV/AIDS-animal models</searchLink><br /><searchLink fieldCode="DE" term="%22human+cancer+xenograft+models%22">human cancer xenograft models</searchLink><br /><searchLink fieldCode="DE" term="%22humanized+immune+system+and+rats%22">humanized immune system and rats</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Animals%22">MESH: Animals</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Cytomegalovirus+Infections+%2F+immunology%22">MESH: Cytomegalovirus Infections / immunology</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Rats%22">MESH: Rats</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Cytomegalovirus+Infections+%2F+prevention+%26+control%22">MESH: Cytomegalovirus Infections / prevention & control</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Cytomegalovirus+Vaccines+%2F+immunology%22">MESH: Cytomegalovirus Vaccines / immunology</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Cytomegalovirus+%2F+immunology%22">MESH: Cytomegalovirus / immunology</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Disease+Models%22">MESH: Disease Models</searchLink><br /><searchLink fieldCode="DE" term="%22Animal%22">Animal</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Humans%22">MESH: Humans</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Mice%22">MESH: Mice</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Neoplasms+%2F+immunology%22">MESH: Neoplasms / immunology</searchLink><br /><searchLink fieldCode="DE" term="%22MESH%3A+Neoplasms+%2F+prevention+%26+control%22">MESH: Neoplasms / prevention & control</searchLink><br /><searchLink fieldCode="DE" term="%22[SDV]Life+Sciences+[q-bio]%22">[SDV]Life Sciences [q-bio]</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: International audience ; 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 translatability of research findings.
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  Data: https://inserm.hal.science/inserm-05117161<br />https://inserm.hal.science/inserm-05117161v1/document<br />https://inserm.hal.science/inserm-05117161v1/file/ijms-26-03082.pdf<br />https://doi.org/10.3390/ijms26073082
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      – SubjectFull: HIV vaccines
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