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© Research
Publication : PLoS pathogens

Repertoire characterization and validation of gB-specific human IgGs directly cloned from humanized mice vaccinated with dendritic cells and protected against HCMV.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in PLoS pathogens - 01 Jul 2020

Theobald SJ, Kreer C, Khailaie S, Bonifacius A, Eiz-Vesper B, Figueiredo C, Mach M, Backovic M, Ballmaier M, Koenig J, Olbrich H, Schneider A, Volk V, Danisch S, Gieselmann L, Ercanoglu MS, Messerle M, Kaisenberg CV, Witte T, Klawonn F, Meyer-Hermann M, Klein F, Stripecke R,

Link to Pubmed [PMID] – 32667948

Link to DOI [DOI] – 10.1371/journal.ppat.1008560

PLoS Pathog 2020 07; 16(7): e1008560

Human cytomegalovirus (HCMV) causes serious complications to immune compromised hosts. Dendritic cells (iDCgB) expressing granulocyte-macrophage colony-stimulating factor, interferon-alpha and HCMV-gB were developed to promote de novo antiviral adaptive responses. Mice reconstituted with a human immune system (HIS) were immunized with iDCgB and challenged with HCMV, resulting into 93% protection. Immunization stimulated the expansion of functional effector memory CD8+ and CD4+ T cells recognizing gB. Machine learning analyses confirmed bone marrow T/CD4+, liver B/IgA+ and spleen B/IgG+ cells as predictive biomarkers of immunization (≈87% accuracy). CD8+ and CD4+ T cell responses against gB were validated. Splenic gB-binding IgM-/IgG+ B cells were sorted and analyzed at a single cell level. iDCgB immunizations elicited human-like IgG responses with a broad usage of various IgG heavy chain V gene segments harboring variable levels of somatic hypermutation. From this search, two gB-binding human monoclonal IgGs were generated that neutralized HCMV infection in vitro. Passive immunization with these antibodies provided proof-of-concept evidence of protection against HCMV infection. This HIS/HCMV in vivo model system supported the validation of novel active and passive immune therapies for future clinical translation.

https://pubmed.ncbi.nlm.nih.gov/32667948