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Modeling Human Cytomegalovirus in Humanized Mice for Vaccine Testing

by Johannes Koenig 1,2,3,†, Sebastian J. Theobald 1,2,3,† and Renata Stripecke 1,2,3,*
Laboratory of Regenerative Immune Therapies Applied, Excellence Cluster REBIRTH, Hannover Medical School, 30625 Hannover, Germany
Clinic of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, 30625 Hannover, Germany
German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 30625 Hannover, Germany
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(1), 89; (registering DOI)
Received: 31 January 2020 / Revised: 12 February 2020 / Accepted: 12 February 2020 / Published: 17 February 2020
(This article belongs to the Special Issue Humanized Mice in Vaccinology: Opportunities and Challenges)
Human cytomegalovirus (HCMV or HHV-5) is a globally spread pathogen with strictly human tropism that establishes a life-long persistence. After primary infection, high levels of long-term T and B cell responses are elicited, but the virus is not cleared. HCMV persists mainly in hematopoietic reservoirs, whereby occasional viral reactivation and spread are well controlled in immunocompetent hosts. However, when the immune system cannot control viral infections or reactivations, such as with newborns, patients with immune deficiencies, or immune-compromised patients after transplantations, the lytic outbursts can be severely debilitating or lethal. The development of vaccines for immunization of immune-compromised hosts has been challenging. Several vaccine candidates did not reach the potency expected in clinical trials and were not approved. Before anti-HCMV vaccines can be tested pre-clinically in immune-compromised hosts, reliable in vivo models recapitulating HCMV infection might accelerate their clinical translation. Therefore, immune-deficient mouse strains implanted with human cells and tissues and developing a human immune system (HIS) are being explored to test anti-HCMV vaccines. HIS-mice resemble immune-compromised hosts as they are equipped with antiviral human T and B cells, but the immune reactivity is overall low. Several groups have independently shown that HCMV infections and reactivations can be mirrored in HIS mice. However, these models and the analyses employed varied widely. The path forward is to improve human immune reconstitution and standardize the analyses of adaptive responses so that HIS models can be forthrightly used for testing novel generations of anti-HCMV vaccines in the preclinical pipeline. View Full-Text
Keywords: CMV; HHV-5; humanized mice; HIS; transplantation; T cells; antibodies; dendritic cells; vaccines CMV; HHV-5; humanized mice; HIS; transplantation; T cells; antibodies; dendritic cells; vaccines
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Koenig, J.; Theobald, S.J.; Stripecke, R. Modeling Human Cytomegalovirus in Humanized Mice for Vaccine Testing. Vaccines 2020, 8, 89.

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