About: HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions

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An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions
Creator	Pollara, Justin Cisneros De La Rosa, Eduardo Huffman, Tori Nelson, Cody Pass, Robert Permar, Sallie Xie, Guanhua
Source	BioRxiv; MedRxiv
abstract	Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful HCMV vaccine tested to-date, demonstrating approximately 50% efficacy in preventing HCMV acquisition in phase II trials. However, the mechanism of vaccine protection remains unknown. Plasma from 33 gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope specificity as well as neutralizing and non-neutralizing anti-HCMV effector functions, and compared to an HCMV-seropositive cohort. gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity comparable to natural infection. Additionally, IgG subclass distribution was similar with predominant IgG1 and IgG3 responses induced by gB vaccination and HCMV infection. However, vaccine-elicited antibodies exhibited limited neutralization of the autologous virus, negligible neutralization of multiple heterologous strains, and limited binding responses against gB structural motifs targeted by neutralizing antibodies including AD-1, AD-2, and Domain I. Interestingly, vaccinees had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating immunodominance against this non-neutralizing, cytosolic region. Finally, vaccine-elicited IgG robustly bound trimeric, membrane-associated gB on the surface of transfected or HCMV-infected cells and mediated virion phagocytosis, though were poor mediators of NK cell activation. Altogether, these data suggest that non-neutralizing antibody functions, including virion phagocytosis, likely played a role in the observed 50% vaccine-mediated protection against HCMV acquisition. The CDC estimates that every hour, a child is born in the United States with permanent neurologic disability resulting from human cytomegalovirus (HCMV) infection – more than is caused by Down syndrome, fetal alcohol syndrome, and neural tube defects combined. A maternal vaccine to block transmission of HCMV to the developing fetus is a necessary intervention to prevent these adverse outcomes. The gB/MF59 vaccine is the most successful tested clinically to-date, achieving 50% reduction in HCMV acquisition. This manuscript establishes the function and epitope specificity of the humoral response stimulated by this vaccine that may explain the partial vaccine efficacy. Understanding the mechanism of gB/MF59-elicited protective immune responses will guide rational design and evaluation of the next generation of HCMV vaccines.
has issue date	2018-01-11(xsd:dateTime)
bibo:doi	10.1101/246884
has license	medrxiv
sha1sum (hex)	2837878533cf5c0521c9ebc530de2ffcfab12a8d
schema:url	https://doi.org/10.1101/246884
resource representing a document's title	HCMV glycoprotein B subunit vaccine efficacy was mediated by non-neutralizing antibody effector functions
schema:publication	bioRxiv
resource representing a document's body	covid:2837878533cf5c0521c9ebc530de2ffcfab12a8d#body_text
is schema:about of	named entity 'Title' named entity 'HCMV' named entity 'antibody' named entity 'word count' named entity 'Short Title' named entity 'CD4+' named entity 'HCMV' named entity 'MF59' named entity 'antibody' named entity 'correlation matrix' named entity 'vaccine' named entity 'glycoprotein' named entity 'vaccine' named entity 'linear epitope' named entity 'humoral response' named entity 'open reading frame' named entity 'peptide microarray' named entity 'HCMV' named entity 'peptide' named entity 'HCMV' named entity 'CD8+ T cells' named entity 'MF59' named entity 'HCMV' named entity 'Assay' named entity 'mononuclear cells' named entity 'antibodies' named entity 'MF59' named entity 'epitope' named entity 'vaccine' named entity 'neural tube defects' named entity 'vaccine' named entity 'virus' named entity 'infection' named entity 'MF59' named entity 'vaccination' named entity 'disability' named entity 'MF59' named entity 'Glycoprotein' named entity 'hearing loss' named entity 'HCMV' named entity 'epitope' named entity 'infection' named entity 'vaccines' named entity 'HCMV' named entity 'adjuvant' named entity 'neurologic' named entity 'HCMV' named entity 'HCMV' named entity 'congenital infection' named entity 'vaccine' named entity 'vaccine' named entity 'correlation matrix' named entity 'vaccine' named entity 'infection' named entity 'vaccination' named entity 'subunit vaccine' named entity 'United States' named entity 'brain damage' named entity 'HCMV' named entity 'CDC' named entity 'antibody' named entity 'phase II trials' named entity 'neutralizing antibodies' named entity 'MF59' named entity 'subunit vaccine' named entity 'amino acid' named entity 'pregnancy' named entity 'vaccine' named entity 'phagocytosis' named entity 'MF59' named entity 'MF59' named entity 'glycoprotein' named entity 'developing fetus' named entity 'human cytomegalovirus' named entity 'Human cytomegalovirus' named entity 'antibodies' named entity 'vaccination' named entity 'vaccine'

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